Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
Intelligent Design
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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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Gene regulatory interactions are of fundamental importance to various biological functions and processes. However, only a few previous computational studies have claimed success in revealing genome-wide regulatory landscapes from temporal gene expression data, especially for complex eukaryotes like human.
A scalable algorithm for structure identification of complex gene regulatory network from temporal expression data. Gui S, Rice AP, Chen R, Wu L, Liu J, Miao H BMC Bioinformatics. 18(1):74. doi: 10.1186/s12859-017-1489-z.

Complex complexity.Dionisio_{March 23, 2017
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[...] detailed studies on conditional Nfil3 deletion in mature ILC subsets need to be performed in order to fully address this question. [...] NFIL3 is a key regulator of the common-helper-like innate lymphoid precursor [...] [...] cytotoxic ILC development, notably NK cells, also rely on NFIL3 [...] [...] NFIL3 may be required for the early establishment of a common helper- and cytotoxic-ILC lineage progenitor [...] [...] NFIL3 can direct the development of a common cytotoxic and helper ILC precursor [...] Genetic fate-mapping studies, multiparametric reporter lines, and lineage-targeted strategies will be central to further elucidate the existence and the fate of such global innate lymphoid progenitor (GILP) to helper and cytotoxic ILCs [...]
NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors. Xu W1, Domingues RG2, Fonseca-Pereira D2, Ferreira M2, Ribeiro H2, Lopez-Lastra S1, Motomura Y3, Moreira-Santos L2, Bihl F4, Braud V4, Kee B5, Brady H6, Coles MC7, Vosshenrich C1, Kubo M8, Di Santo JP9, Veiga-Fernandes H10 Cell Rep. 10(12):2043-54. doi: 10.1016/j.celrep.2015.02.057.

Complex complexity.Dionisio_{March 23, 2017
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The relationship between ?LP and CHILP is unclear, but it is possible that NFIL3 may act by distinct mechanisms in different ILC precursors. A potent cell-intrinsic role for NFIL3 in the generation of all recognized ILC subsets, including NK cells [...] and ILC1, ILC2, and ILC3 [...] has recently been reported. [...] NFIL3 directly regulated Id2 in CHILP. [...] cytokine-dependent signals may promote stabilization and/or enhancement of NFIL3, which in turn orchestrates the emergence of CHILP via direct Id2 regulation. [...] NFIL3 may also play additional context-dependent roles at later stages of ILC differentiation and for maintenance of effector functions in mature ILC subsets.
NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors. Xu W1, Domingues RG2, Fonseca-Pereira D2, Ferreira M2, Ribeiro H2, Lopez-Lastra S1, Motomura Y3, Moreira-Santos L2, Bihl F4, Braud V4, Kee B5, Brady H6, Coles MC7, Vosshenrich C1, Kubo M8, Di Santo JP9, Veiga-Fernandes H10 Cell Rep. 10(12):2043-54. doi: 10.1016/j.celrep.2015.02.057.

Did somebody say "orchestrates"? :) Complex complexity.Dionisio_{March 23, 2017
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The development of multiple and distinct hematopoietic cell lineages relies on tightly controlled expression of transcription factors that promote lineage specification and commitment while suppressing alternative cell fates. [...] how the emergence of CHILP from CLP is regulated remains elusive. [...] it is not clear how Id2 expression is regulated in lymphoid progenitors (CLP) or how titration and reduction of E-protein activity allows for emergence of CHILP from these cells. [...] the molecular basis for the NFIL3 effect remained unclear. [...] NFIL3 is a critical regulator of the common-helper-like ILC progenitor (CHILP), while being dispensable for overall helper-like ILC fate and maintenance of discrete mature ILC subsets [...] [...] NFIL3 emerges as a central regulator of the common helper ILC precursor in early lymphopoiesis.
NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors. Xu W1, Domingues RG2, Fonseca-Pereira D2, Ferreira M2, Ribeiro H2, Lopez-Lastra S1, Motomura Y3, Moreira-Santos L2, Bihl F4, Braud V4, Kee B5, Brady H6, Coles MC7, Vosshenrich C1, Kubo M8, Di Santo JP9, Veiga-Fernandes H10 Cell Rep. 10(12):2043-54. doi: 10.1016/j.celrep.2015.02.057.

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#2953 addendum:
The immune system is composed by myriads of cell types and lymphoid organs that ensure immune surveillance and protective immunity. The adaptive immune system [...] consists of B and T lymphocytes that express recombining antigen-specific receptors. Naive T and B cells are activated by their cognate antigen in secondary lymphoid organs and undergo significant cell division and differentiation before exerting their effector function. In contrast, innate lymphocytes display rapid effector functions despite their set of limited germ-line-encoded receptors.
NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors. Xu W1, Domingues RG2, Fonseca-Pereira D2, Ferreira M2, Ribeiro H2, Lopez-Lastra S1, Motomura Y3, Moreira-Santos L2, Bihl F4, Braud V4, Kee B5, Brady H6, Coles MC7, Vosshenrich C1, Kubo M8, Di Santo JP9, Veiga-Fernandes H10 Cell Rep. 10(12):2043-54. doi: 10.1016/j.celrep.2015.02.057.

Complex complexity.Dionisio_{March 23, 2017
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In the developing brain, miR-9 influences gene expression, proliferation, neurogenesis, maturation, migration, and differentiation in a spatiotemporal pattern. There are also feedback loop mechanisms for Tlx, Foxg1, and Foxp1 with miR-9 that regulates cellular events within the developing vertebrate brain. Further studies are required to completely understand the role of miR-9 in vertebrate brain development. [...] miR-9 is necessary for the development of the embryonic brain.
Role of miRNA-9 in Brain Development. Radhakrishnan B, Alwin Prem Anand A J Exp Neurosci. 10:101-120. DOI: 10.4137/JEN.S32843

Complex complexity.Dionisio_{March 22, 2017
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MicroRNAs (miRNAs) are a class of small regulatory RNAs involved in gene regulation. The regulation is effected by either translational inhibition or transcriptional silencing. In vertebrates, the importance of miRNA in development was discovered from mice and zebrafish dicer knockouts. The miRNA-9 (miR-9) is one of the most highly expressed miRNAs in the early and adult vertebrate brain. It has diverse functions within the developing vertebrate brain. In vertebrate brain development, miR-9 is involved in regulating several region-specific genes in a spatiotemporal pattern.
Role of miRNA-9 in Brain Development. Radhakrishnan B, Alwin Prem Anand A J Exp Neurosci. 10:101-120. DOI: 10.4137/JEN.S32843

Complex complexity.Dionisio_{March 22, 2017
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Innate lymphoid cells (ILCs) are a family of effectors that originate from a common innate lymphoid cell progenitor. However, the transcriptional program that sets the identity of the ILC lineage remains elusive. NFIL3 is a critical regulator of the common helper-like innate lymphoid cell progenitor (CHILP).
NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors. Xu W1, Domingues RG2, Fonseca-Pereira D2, Ferreira M2, Ribeiro H2, Lopez-Lastra S1, Motomura Y3, Moreira-Santos L2, Bihl F4, Braud V4, Kee B5, Brady H6, Coles MC7, Vosshenrich C1, Kubo M8, Di Santo JP9, Veiga-Fernandes H10 Cell Rep. 10(12):2043-54. doi: 10.1016/j.celrep.2015.02.057.

Complex complexity.Dionisio_{March 22, 2017
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Even though NK cells are mainly known as killer cells of the innate immune system, there is more and more evidence that NK cells can shape the adaptive immune system by influencing T cells in different stages of their lifespan. More detailed insight into the detailed mechanisms of DC/NK interaction will be important to tailor T cell immunity in the context of vaccination or toleration. The absence of NK cells induces alterations in the early phase of T cell responses, including direct attack of T cells. The detailed mechanisms of this direct regulation are, however, still being defined. [...] more insights into the regulation of NK receptor ligand expression on activated T cells is required. [...] a more detailed molecular understanding about this shielding process is important. Such knowledge might also be useful to understand whether and how autoreactive T cells can be rendered targets for NK cell attack.
Recognition and Regulation of T Cells by NK Cells. Pallmer K, Oxenius A Front Immunol. 7:251. doi: 10.3389/fimmu.2016.00251

Complex complexity.Dionisio_{March 22, 2017
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Regulation of T cell responses by innate lymphoid cells (ILCs) is increasingly documented and studied. Direct or indirect crosstalk between ILCs and T cells early during and after T cell activation can affect their differentiation, polarization, and survival. Natural killer (NK) cells, presenting at a frequency of around 5% in the blood, belong to the family of group 1 innate lymphocytes (ILC1) and are functionally characterized by their cytotoxicity and their ability to produce cytokines, most prominently interferon ? (IFN?). NK cells belong to the innate immune system, and they can react to rapid changes in host cells without prior sensitization.
Recognition and Regulation of T Cells by NK Cells. Pallmer K, Oxenius A Front Immunol. 7:251. doi: 10.3389/fimmu.2016.00251

Complex complexity.Dionisio_{March 22, 2017
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[...] it will be important to further investigate the mechanisms by which ILCs prevent or promote T cell responses in various tissues. [...] it will be interesting to unravel whether ILCs can express inhibitory receptors and/or collaborate with Treg cells. [...] a better understanding of the regulation of cytokine expression by ILCs and their interaction with T cells will help to develop new strategies to treat inflammatory diseases in humans.
Maintenance of Immune Homeostasis through ILC/T Cell Interactions. von Burg N, Turchinovich G, Finke D Front Immunol. 6:416. doi: 10.3389/fimmu.2015.00416

Complex complexity.Dionisio_{March 22, 2017
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[...] several CD4+ TH cells are often clustering with the same APC, a fact that may increase local cytokine concentrations for optimal cell–cell interactions.
Maintenance of Immune Homeostasis through ILC/T Cell Interactions. von Burg N, Turchinovich G, Finke D Front Immunol. 6:416. doi: 10.3389/fimmu.2015.00416

Do those cells do things for a "purpose"? :) Complex complexity.Dionisio_{March 22, 2017
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Considering the fact that the number of ILCs in most tissues is rather low as compared to other immune cells, they appear to have a surprising in vivo impact on immune homeostasis. The localization of ILCs in relatively high density at Ag-entry sites and T cell areas as well as bystander effects on classical DCs might explain this effect.
Maintenance of Immune Homeostasis through ILC/T Cell Interactions. von Burg N, Turchinovich G, Finke D Front Immunol. 6:416. doi: 10.3389/fimmu.2015.00416

Did somebody say "surprising"? :) Complex complexity.Dionisio_{March 22, 2017
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Our understanding of immune homeostasis has been challenged by the notion that environmental factors, including commensal bacteria and nutritional components, as well as cholinergic and metabolic signals can regulate immune functions and pro-inflammatory processes. ILCs are important “early sentinel” cells, which connect innate and adaptive immunity by sensing environmental changes, such as infections and inflammation and by the release of immuno-regulatory cytokines.
Maintenance of Immune Homeostasis through ILC/T Cell Interactions. von Burg N, Turchinovich G, Finke D Front Immunol. 6:416. doi: 10.3389/fimmu.2015.00416

Complex complexity.Dionisio_{March 22, 2017
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Adaptive immune responses are tightly controlled by the selection of the T and B cell receptor repertoire and by transcriptional networks regulating commitment, expansion, and contraction of the responses. Upon cognate antigen (Ag)–peptide–major histocompatibility complex (MHC) recognition Ag-specific T helper (TH) cells proliferate and differentiate into effector TH cell subsets with distinguishable cytokine profiles. In the past 5 years, new subsets of innate immune cells have emerged as a first line of defense at mucosal barriers. Like conventional natural killer (cNK) cells, they belong to the lymphoid lineage and develop from common lymphoid progenitor (CLP) cells but unlike T and B cells, they lack rearranged Ag-receptors. Hence, they were termed innate lymphoid cells (ILCs).
Maintenance of Immune Homeostasis through ILC/T Cell Interactions. von Burg N, Turchinovich G, Finke D Front Immunol. 6:416. doi: 10.3389/fimmu.2015.00416

Complex complexity.Dionisio_{March 22, 2017
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Both ILC2s and ILC3s are able to process and present foreign antigens (Ags) via major histocompatibility complex class II, and to induce cognate CD4(+) T cell responses. In addition, Ag-stimulated T cells promote ILC activation and effector functions indicating a reciprocal interaction between the adaptive and innate immune system. A fundamental puzzle in ILC function is how ILC/T cell interactions promote host protection and prevent autoimmune diseases. Furthermore, the way in which microenvironmental and inflammatory signals determine the outcome of ILC/T cell immune responses in various tissues is not yet understood.
Maintenance of Immune Homeostasis through ILC/T Cell Interactions. von Burg N, Turchinovich G, Finke D Front Immunol. 6:416. doi: 10.3389/fimmu.2015.00416

Did somebody say "fundamental puzzle"? :) Complex complexity.Dionisio_{March 22, 2017
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Innate lymphoid cells (ILCs) have emerged as a new family of immune cells with crucial functions in innate and adaptive immunity. ILC subsets mirror the cytokine and transcriptional profile of CD4(+) T helper (TH) cell subsets. Hence, group 1 (ILC1), group 2 (ILC2), and group 3 (ILC3) ILCs can be distinguished by the production of TH1, TH2, and TH17-type cytokines, respectively. Cytokine release by ILCs not only shapes early innate immunity but can also orchestrate TH immune responses to microbial or allergen exposure.
Maintenance of Immune Homeostasis through ILC/T Cell Interactions. von Burg N, Turchinovich G, Finke D Front Immunol. 6:416. doi: 10.3389/fimmu.2015.00416

Did somebody say "orchestrate"? :) Complex complexity.Dionisio_{March 22, 2017
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The discovery of the ILCs in recent years together with a deeper understanding of their biology has led to a major paradigm shift in the study of immunity and hematopoiesis. Many of the transcription factors that programme TH cell differentiation are also conserved in the ILCs but the cues for switching them on, and when they can be replaced or substituted by another transcription factor are not completely understood. These aspects of ILC development form exciting research questions for future investigation.
Deciphering the transcriptional switches of innate lymphoid cell programming: the right factors at the right time. Lim AW, McKenzie AN Genes Immun. 16(3):177-86. doi: 10.1038/gene.2014.83.

Did somebody say “major paradigm shift”? Complex complexity.Dionisio_{March 22, 2017
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Transcriptional programming of immune cell fate and lineage specificity is essential for the commitment and development of the hematopoietic system. Innate lymphoid cells (ILCs) are increasingly recognised as an innate immune counterpart of adaptive TH cells. Natural killer cells, which are the cytotoxic ILCs, develop along a pathway distinct from the rest of the helper-like ILCs that are derived from a common progenitor to all helper-like innate lymphoid cells (CHILPs). PLZF? CHILPs give rise to lymphoid tissue inducer cells while PLZF+ CHILPs have multi-lineage potential and could give rise to ILCs 1, 2 and 3. Such lineage specificity is dictated by the controlled expression of T-bet, ROR?, ROR?t and AHR. In addition to the type of transcription factors, the developmental stages at which these factors are expressed are crucial in specifying the fate of the ILCs.
Deciphering the transcriptional switches of innate lymphoid cell programming: the right factors at the right time. Lim AW, McKenzie AN Genes Immun. 16(3):177-86. doi: 10.1038/gene.2014.83.

Did somebody say “programming”? Complex complexity.Dionisio_{March 22, 2017
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Surprisingly, we found that the loss of NFIL3 function in cells expressing ID2 did not significantly affect the subsequent development of ILC subsets. Collectively, our data establish a genome-wide transcriptional blueprint of the different ILC progenitors and uncover potentially important transcriptional regulators that are likely to reveal key insights into ILC development and interactions with other immune cells in the tissue.
Deciphering the Innate Lymphoid Cell Transcriptional Program. Seillet C, Mielke LA, Amann-Zalcenstein DB, Su S, Gao J, Almeida FF, Shi W, Ritchie ME, Naik SH, Huntington ND, Carotta S, Belz GT Cell Rep. 17(2):436-447. doi: 10.1016/j.celrep.2016.09.025.

Did somebody say "surprisingly"? Complex complexity.Dionisio_{March 22, 2017
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Innate lymphoid cells (ILCs) are enriched at mucosal surfaces and sense inflammatory signals to provide protection from mechanical and pathogenic insults through rapid secretion of cytokines. They develop initially from progenitors in the fetal liver [...] later, in the adult bone marrow (BM) [...] [...] exactly how the molecular cues of each of these factors are integrated and drive commitment remains unclear. Collectively, we define the transcriptional landscape of ILC precursors and provide insight into the interplay of transcription factors, particularly the hierarchical interactions, among Id2, Nfil3, and Tcf7 utilized by progenitor cells to generate ILC populations.
Deciphering the Innate Lymphoid Cell Transcriptional Program. Seillet C, Mielke LA, Amann-Zalcenstein DB, Su S, Gao J, Almeida FF, Shi W, Ritchie ME, Naik SH, Huntington ND, Carotta S, Belz GT Cell Rep. 17(2):436-447. doi: 10.1016/j.celrep.2016.09.025.

Complex complexity.Dionisio_{March 22, 2017
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Innate lymphoid cells (ILCs) are enriched at mucosal surfaces, where they provide immune surveillance. All ILC subsets develop from a common progenitor that gives rise to pre-committed progenitors for each of the ILC lineages. Currently, the temporal control of gene expression that guides the emergence of these progenitors is poorly understood. [...] the timing and order of expression of the transcription factors NFIL3, ID2, and TCF-1 was critical. [...] induction of ILC lineage commitment required only transient expression of NFIL3 prior to ID2 and TCF-1 expression. These findings highlight the importance of the temporal program that permits commitment of progenitors to the ILC lineage, and they expand our understanding of the core transcriptional program by identifying potential regulators of ILC development.
Deciphering the Innate Lymphoid Cell Transcriptional Program. Seillet C, Mielke LA, Amann-Zalcenstein DB, Su S, Gao J, Almeida FF, Shi W, Ritchie ME, Naik SH, Huntington ND, Carotta S, Belz GT Cell Rep. 17(2):436-447. doi: 10.1016/j.celrep.2016.09.025.

Complex complexity.Dionisio_{March 22, 2017
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Group 2 innate lymphoid cells (ILC2s) are a recently identified group of cells with the potent capability to produce Th2-type cytokines such as interleukin (IL)-5 and IL-13. Altogether, these new findings uncover iTregs as potent regulators of ILC2 activation and implicate their utility as a therapeutic approach for the treatment of ILC2-mediated allergic asthma and respiratory disease.
Regulatory T cells and type 2 innate lymphoid cell-dependent asthma J. L. Aron, O. Akbari DOI: 10.1111/all.13139View European Journal of Allergy and Clinical Immunology http://onlinelibrary.wiley.com/doi/10.1111/all.13139/full

This is a very interesting example of the translation of biology research discoveries to clinical applications in more effective precise personalized treatments. BTW, had we remained in Eden, none of this would have been an issue. Oh, well. Too late now. Complex complexity.Dionisio_{March 22, 2017
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Taken together, these observations reveal the potential for novel mechanisms of ILC2 and ILC3 cell activation under inflammatory conditions. In summary, this study provides a global, comprehensive, and detailed description of human heterogeneity in ILCs across patients, tissues, in non-pathological conditions, and within various pathological environments. Despite a homology with mice, our study highlights the uniqueness of human ILCs in terms of their composition, phenotypes, and heterogeneity.
Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency Yannick Simoni'Correspondence information about the author Yannick SimoniEmail the author Yannick Simoni, Michael Fehlings, Henrik N. Kløverpris, Naomi McGovern, Si-Lin Koo, Chiew Yee Loh, Shawn Lim, Ayako Kurioka, Joannah R. Fergusson, Choong-Leong Tang, Ming Hian Kam, Koh Dennis, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Chan Weng Hoong, Jerry Kok Yen Chan, Maria Curotto de Lafaille, Sriram Narayanan, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow Toh, Henry Kun Kiaang Tan, Rosslyn Anicete, Eng-Huat Tan, Angela Takano, Paul Klenerman, Alasdair Leslie, Daniel S.W. Tan, Iain Beehuat Tan, Florent Ginhoux, Evan W. Newell DOI: 10.1016/j.immuni.2016.11.005 Immunity, Volume 46, Issue 1, p148–161

Did somebody say "uniqueness of human [...]"? :) Complex complexity.Dionisio_{March 22, 2017
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Across all tissues studied, we were unable to clearly detect MHC II expression by ILCs. As compared to mice, this observation can be explained by different molecular mechanisms regulating MHCII expression in humans [...] [...] MHC II expression on ILCs is restricted to some specific inflammatory conditions.
Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency Yannick Simoni'Correspondence information about the author Yannick SimoniEmail the author Yannick Simoni, Michael Fehlings, Henrik N. Kløverpris, Naomi McGovern, Si-Lin Koo, Chiew Yee Loh, Shawn Lim, Ayako Kurioka, Joannah R. Fergusson, Choong-Leong Tang, Ming Hian Kam, Koh Dennis, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Chan Weng Hoong, Jerry Kok Yen Chan, Maria Curotto de Lafaille, Sriram Narayanan, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow Toh, Henry Kun Kiaang Tan, Rosslyn Anicete, Eng-Huat Tan, Angela Takano, Paul Klenerman, Alasdair Leslie, Daniel S.W. Tan, Iain Beehuat Tan, Florent Ginhoux, Evan W. Newell DOI: 10.1016/j.immuni.2016.11.005 Immunity, Volume 46, Issue 1, p148–161

Humans have different molecular regulatory mechanisms for equivalent genetic expression? Hmm... interesting. This may help: https://ghr.nlm.nih.gov/primer/genefamily/hla Complex complexity.Dionisio_{March 22, 2017
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[...] human tissues can be divided into two categories based on their overall ILC subsets composition. [...] ILC2 cells found in cord blood are functionally similar to ILC2 cells derived from adult blood when stimulated with IL-33. In contrast to non-mucosal and lung tissues, oral and gastrointestinal mucosal and skin tissues contained high frequencies of helper-type ILCs [...] [...] observations about helper type ILC phenotypes could be considered as additional targets for therapeutics approaches.
Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency Yannick Simoni'Correspondence information about the author Yannick SimoniEmail the author Yannick Simoni, Michael Fehlings, Henrik N. Kløverpris, Naomi McGovern, Si-Lin Koo, Chiew Yee Loh, Shawn Lim, Ayako Kurioka, Joannah R. Fergusson, Choong-Leong Tang, Ming Hian Kam, Koh Dennis, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Chan Weng Hoong, Jerry Kok Yen Chan, Maria Curotto de Lafaille, Sriram Narayanan, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow Toh, Henry Kun Kiaang Tan, Rosslyn Anicete, Eng-Huat Tan, Angela Takano, Paul Klenerman, Alasdair Leslie, Daniel S.W. Tan, Iain Beehuat Tan, Florent Ginhoux, Evan W. Newell DOI: 10.1016/j.immuni.2016.11.005 Immunity, Volume 46, Issue 1, p148–161

Complex complexity.Dionisio_{March 22, 2017
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[...] a large number of markers was required for this detailed and accurate characterization of putative ILC1 cells [...] [...] it might be possible that previous identifications of human ILC1 cells comprised cellular contaminations, which could not be excluded due to technical limitations.
Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency Yannick Simoni'Correspondence information about the author Yannick SimoniEmail the author Yannick Simoni, Michael Fehlings, Henrik N. Kløverpris, Naomi McGovern, Si-Lin Koo, Chiew Yee Loh, Shawn Lim, Ayako Kurioka, Joannah R. Fergusson, Choong-Leong Tang, Ming Hian Kam, Koh Dennis, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Chan Weng Hoong, Jerry Kok Yen Chan, Maria Curotto de Lafaille, Sriram Narayanan, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow Toh, Henry Kun Kiaang Tan, Rosslyn Anicete, Eng-Huat Tan, Angela Takano, Paul Klenerman, Alasdair Leslie, Daniel S.W. Tan, Iain Beehuat Tan, Florent Ginhoux, Evan W. Newell DOI: 10.1016/j.immuni.2016.11.005 Immunity, Volume 46, Issue 1, p148–161

Complex complexity.Dionisio_{March 22, 2017
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[...] helper-type ILCs can be subdivided into three main groups analogous to the main subsets of T helper lymphocytes. ILC1 cells can produce T helper-1 (Th1) cell signature cytokines (i.e., IFN-g) and express the transcription factor T-bet [...] ILC2 cells are capable of secreting Th2 cell-type cytokines and display aGATA3+ phenotype. ILC3 cells have been shown to be associated with interleukin-17 (IL-17) and IL-22 production, as well as RORgt transcription factor expression, characteristic of Th17 helper T cells [...] [...] similar to ILC2 cells, ILC3 cells express CD127 (IL-7R), which is crucial for their development and survival [...]
Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency Yannick Simoni'Correspondence information about the author Yannick SimoniEmail the author Yannick Simoni, Michael Fehlings, Henrik N. Kløverpris, Naomi McGovern, Si-Lin Koo, Chiew Yee Loh, Shawn Lim, Ayako Kurioka, Joannah R. Fergusson, Choong-Leong Tang, Ming Hian Kam, Koh Dennis, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Chan Weng Hoong, Jerry Kok Yen Chan, Maria Curotto de Lafaille, Sriram Narayanan, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow Toh, Henry Kun Kiaang Tan, Rosslyn Anicete, Eng-Huat Tan, Angela Takano, Paul Klenerman, Alasdair Leslie, Daniel S.W. Tan, Iain Beehuat Tan, Florent Ginhoux, Evan W. Newell DOI: 10.1016/j.immuni.2016.11.005 Immunity, Volume 46, Issue 1, p148–161

Complex complexity.Dionisio_{March 22, 2017
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[...] human ILCs are highly heterogeneous cell types between individuals and tissues. Innate lymphoid cells (ILCs) represent a heterogeneous population of innate immune cells in mice and humans that include classically defined natural killer (NK) cells as well as more recently described helper-type ILCs (ILC1, ILC2, and ILC3). In contrast to T- and B-lymphocytes, ILCs lack somatic rearrangement of antigen receptors (e.g., TCR,BCR), and can be activated by cytokines and/or through natural cytotoxicity receptors (e.g., NKp44) [...] In contrast to NK cells, helper-type ILCs do not possess efficient cytotoxic capacity [...]
Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency Yannick Simoni'Correspondence information about the author Yannick SimoniEmail the author Yannick Simoni, Michael Fehlings, Henrik N. Kløverpris, Naomi McGovern, Si-Lin Koo, Chiew Yee Loh, Shawn Lim, Ayako Kurioka, Joannah R. Fergusson, Choong-Leong Tang, Ming Hian Kam, Koh Dennis, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Chan Weng Hoong, Jerry Kok Yen Chan, Maria Curotto de Lafaille, Sriram Narayanan, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow Toh, Henry Kun Kiaang Tan, Rosslyn Anicete, Eng-Huat Tan, Angela Takano, Paul Klenerman, Alasdair Leslie, Daniel S.W. Tan, Iain Beehuat Tan, Florent Ginhoux, Evan W. Newell DOI: 10.1016/j.immuni.2016.11.005 Immunity, Volume 46, Issue 1, p148–161

Complex complexity.Dionisio_{March 22, 2017
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Integration of the accumulating knowledge on microbial community structure in different disease scenarios with the corresponding changes in the metabolome and its bioactivity may enable addressing fundamental questions regarding the molecular mechanisms by which the microbiome impacts physiology, pathophysiology and even its own community function
Microbiome-Modulated Metabolites at the Interface of Host Immunity Eran Blacher, Maayan Levy, Evgeny Tatirovsky and Eran Elinav DOI: 10.4049/jimmunol.1601247 J Immunol 2017; 198:572-580 http://www.jimmunol.org/content/198/2/572

Complex complexity.Dionisio_{March 21, 2017
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