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Transcriptional Regulatory Network for the Development of Innate Lymphoid Cells.

Zhong C, Zhu J - Mediators Inflamm. (2015)

Bottom Line: With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells.Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development.We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
Recent studies on innate lymphoid cells (ILCs) have expanded our knowledge about the innate arm of the immune system. Helper-like ILCs share both the "innate" feature of conventional natural killer (cNK) cells and the "helper" feature of CD4(+) T helper (Th) cells. With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells. Although many studies have revealed the functional similarity between helper-like ILCs and Th cells, some aspects of ILCs including the development of this lineage remain elusive. It is intriguing that the majority of transcription factors involved in multiple stages of T cell development, differentiation, and function also play critical roles during ILC development. Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development. In this review, we will summarize the expression and functions of these transcription factors shared by ILCs and Th cells. We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs.

No MeSH data available.


Parallels between the development of innate lymphocytes and T cells. Lymphoid DCs, B cells, T cells, and innate lymphocytes including ILCs and cNK cells are derived from common lymphoid progenitors (CLPs). While innate lymphocytes mainly develop in the bone marrow, T cells develop in the thymus. T cell development passes through a fate determination (from ETP/DN1 to DN2 to DN3) stage before CD4+ and CD8+ T cells develop separately from progenitor-like CD4+CD8+ DP cells. After CD4+ T cell development, effector Th cells are differentiated from naïve CD4+ T cells upon activation. In parallel, for the innate lymphocyte development, there may also be a stage when the innate fate is determined followed by the generation of ILC and cNK common progenitors. ILC and cNK lineage then develop separately under the guidance of distinct master regulators. Similar to effector Th cells differentiating from naïve CD4+ T cells, all mature ILC subsets also develop from a common progenitor. Therefore, ILCs share with T cells in utilizing multiple transcription factors at similar stages during their development/differentiation.
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fig1: Parallels between the development of innate lymphocytes and T cells. Lymphoid DCs, B cells, T cells, and innate lymphocytes including ILCs and cNK cells are derived from common lymphoid progenitors (CLPs). While innate lymphocytes mainly develop in the bone marrow, T cells develop in the thymus. T cell development passes through a fate determination (from ETP/DN1 to DN2 to DN3) stage before CD4+ and CD8+ T cells develop separately from progenitor-like CD4+CD8+ DP cells. After CD4+ T cell development, effector Th cells are differentiated from naïve CD4+ T cells upon activation. In parallel, for the innate lymphocyte development, there may also be a stage when the innate fate is determined followed by the generation of ILC and cNK common progenitors. ILC and cNK lineage then develop separately under the guidance of distinct master regulators. Similar to effector Th cells differentiating from naïve CD4+ T cells, all mature ILC subsets also develop from a common progenitor. Therefore, ILCs share with T cells in utilizing multiple transcription factors at similar stages during their development/differentiation.

Mentions: Given the functional similarities between the innate ILCs and cNK cells and the adaptive CD4 and CD8 T cells, it is reasonable to propose that ILCs and cNK cells follow a similar developmental pathway to that of T cells. A CLP may give rise to a common progenitor for all innate lymphocytes including ILCs and cNK cells, which subsequently gives rise to ChILPs. Distinct ILC subsets are further developed from the PLZF+ ChILP stage as the differentiation of Th effectors from naïve CD4+ T cells. Thus, the development of innate lymphocyte subsets, including ILCs and cNK cells, to a certain extent, mirrors that of T cells (Figure 1).


Transcriptional Regulatory Network for the Development of Innate Lymphoid Cells.

Zhong C, Zhu J - Mediators Inflamm. (2015)

Parallels between the development of innate lymphocytes and T cells. Lymphoid DCs, B cells, T cells, and innate lymphocytes including ILCs and cNK cells are derived from common lymphoid progenitors (CLPs). While innate lymphocytes mainly develop in the bone marrow, T cells develop in the thymus. T cell development passes through a fate determination (from ETP/DN1 to DN2 to DN3) stage before CD4+ and CD8+ T cells develop separately from progenitor-like CD4+CD8+ DP cells. After CD4+ T cell development, effector Th cells are differentiated from naïve CD4+ T cells upon activation. In parallel, for the innate lymphocyte development, there may also be a stage when the innate fate is determined followed by the generation of ILC and cNK common progenitors. ILC and cNK lineage then develop separately under the guidance of distinct master regulators. Similar to effector Th cells differentiating from naïve CD4+ T cells, all mature ILC subsets also develop from a common progenitor. Therefore, ILCs share with T cells in utilizing multiple transcription factors at similar stages during their development/differentiation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4563091&req=5

fig1: Parallels between the development of innate lymphocytes and T cells. Lymphoid DCs, B cells, T cells, and innate lymphocytes including ILCs and cNK cells are derived from common lymphoid progenitors (CLPs). While innate lymphocytes mainly develop in the bone marrow, T cells develop in the thymus. T cell development passes through a fate determination (from ETP/DN1 to DN2 to DN3) stage before CD4+ and CD8+ T cells develop separately from progenitor-like CD4+CD8+ DP cells. After CD4+ T cell development, effector Th cells are differentiated from naïve CD4+ T cells upon activation. In parallel, for the innate lymphocyte development, there may also be a stage when the innate fate is determined followed by the generation of ILC and cNK common progenitors. ILC and cNK lineage then develop separately under the guidance of distinct master regulators. Similar to effector Th cells differentiating from naïve CD4+ T cells, all mature ILC subsets also develop from a common progenitor. Therefore, ILCs share with T cells in utilizing multiple transcription factors at similar stages during their development/differentiation.
Mentions: Given the functional similarities between the innate ILCs and cNK cells and the adaptive CD4 and CD8 T cells, it is reasonable to propose that ILCs and cNK cells follow a similar developmental pathway to that of T cells. A CLP may give rise to a common progenitor for all innate lymphocytes including ILCs and cNK cells, which subsequently gives rise to ChILPs. Distinct ILC subsets are further developed from the PLZF+ ChILP stage as the differentiation of Th effectors from naïve CD4+ T cells. Thus, the development of innate lymphocyte subsets, including ILCs and cNK cells, to a certain extent, mirrors that of T cells (Figure 1).

Bottom Line: With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells.Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development.We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
Recent studies on innate lymphoid cells (ILCs) have expanded our knowledge about the innate arm of the immune system. Helper-like ILCs share both the "innate" feature of conventional natural killer (cNK) cells and the "helper" feature of CD4(+) T helper (Th) cells. With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells. Although many studies have revealed the functional similarity between helper-like ILCs and Th cells, some aspects of ILCs including the development of this lineage remain elusive. It is intriguing that the majority of transcription factors involved in multiple stages of T cell development, differentiation, and function also play critical roles during ILC development. Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development. In this review, we will summarize the expression and functions of these transcription factors shared by ILCs and Th cells. We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs.

No MeSH data available.