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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.


A potential transcriptional regulatory network determining the generation of a common ILC progenitor. Critical transcription factors during common ILC progenitor development are expressed at various stages. After the CLP stage, Nfil3 expression increases followed by Id2 and TOX induction. TOX then induces Notch, which is required for TCF-1 and GATA-3 upregulation. TCF-1 further enhances GATA-3 expression. Although it has not been reported, TCF-1 may also play a role in enhancing Id2 expression. The regulatory network eventually results in optimal Id2 and GATA-3 expression in the common ILC progenitors. Once Id2 and GATA-3 expression reaches a threshold, they orchestrate the acquisition of the “innate” and “helper” features of the ILCs, possibly also with assistance from other transcription factors.
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Related In: Results  -  Collection


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fig2: A potential transcriptional regulatory network determining the generation of a common ILC progenitor. Critical transcription factors during common ILC progenitor development are expressed at various stages. After the CLP stage, Nfil3 expression increases followed by Id2 and TOX induction. TOX then induces Notch, which is required for TCF-1 and GATA-3 upregulation. TCF-1 further enhances GATA-3 expression. Although it has not been reported, TCF-1 may also play a role in enhancing Id2 expression. The regulatory network eventually results in optimal Id2 and GATA-3 expression in the common ILC progenitors. Once Id2 and GATA-3 expression reaches a threshold, they orchestrate the acquisition of the “innate” and “helper” features of the ILCs, possibly also with assistance from other transcription factors.

Mentions: Based on the sequential expression of Nfil3, TOX, TCF-1, Id2, and GATA-3 and the knowledge we have concerning their relationships in different systems, it is likely that Nfil3 expression initially increases after the CLP stage, which in turn regulates the expression of TOX and Id2. After Id2 is turned on, the core assembly involved in directing the “innate” features of ILC development begins to function. Although GATA-3 is expressed at low levels at the CLP stage, its function during ILC development requires high expression levels. TOX is involved in the regulation of Notch signaling pathway, which in turn regulates TCF-1 and GATA-3. TCF-1 is then required for optimal expression of GATA-3. Upon increased expression of GATA-3, the “helper” transcription factor assembly would execute the gene expression program needed for ILC function. In this way, Nfil3, TOX, and TCF-1, in connection with the Notch pathways, form a network to prepare for the upregulation of Id2 and GATA-3, which together form the executive regulatory network to direct lineage fate determination of ILCs, possibly with continued assistance from the initiation transcription factors such as Tcf7, Tox, and Nfil3 (Figure 2). Additional experiments are required to confirm this proposed regulatory network model and it is likely that additional regulators for ILC development may soon be discovered.


Transcriptional Regulatory Network for the Development of Innate Lymphoid Cells.

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

A potential transcriptional regulatory network determining the generation of a common ILC progenitor. Critical transcription factors during common ILC progenitor development are expressed at various stages. After the CLP stage, Nfil3 expression increases followed by Id2 and TOX induction. TOX then induces Notch, which is required for TCF-1 and GATA-3 upregulation. TCF-1 further enhances GATA-3 expression. Although it has not been reported, TCF-1 may also play a role in enhancing Id2 expression. The regulatory network eventually results in optimal Id2 and GATA-3 expression in the common ILC progenitors. Once Id2 and GATA-3 expression reaches a threshold, they orchestrate the acquisition of the “innate” and “helper” features of the ILCs, possibly also with assistance from other transcription factors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: A potential transcriptional regulatory network determining the generation of a common ILC progenitor. Critical transcription factors during common ILC progenitor development are expressed at various stages. After the CLP stage, Nfil3 expression increases followed by Id2 and TOX induction. TOX then induces Notch, which is required for TCF-1 and GATA-3 upregulation. TCF-1 further enhances GATA-3 expression. Although it has not been reported, TCF-1 may also play a role in enhancing Id2 expression. The regulatory network eventually results in optimal Id2 and GATA-3 expression in the common ILC progenitors. Once Id2 and GATA-3 expression reaches a threshold, they orchestrate the acquisition of the “innate” and “helper” features of the ILCs, possibly also with assistance from other transcription factors.
Mentions: Based on the sequential expression of Nfil3, TOX, TCF-1, Id2, and GATA-3 and the knowledge we have concerning their relationships in different systems, it is likely that Nfil3 expression initially increases after the CLP stage, which in turn regulates the expression of TOX and Id2. After Id2 is turned on, the core assembly involved in directing the “innate” features of ILC development begins to function. Although GATA-3 is expressed at low levels at the CLP stage, its function during ILC development requires high expression levels. TOX is involved in the regulation of Notch signaling pathway, which in turn regulates TCF-1 and GATA-3. TCF-1 is then required for optimal expression of GATA-3. Upon increased expression of GATA-3, the “helper” transcription factor assembly would execute the gene expression program needed for ILC function. In this way, Nfil3, TOX, and TCF-1, in connection with the Notch pathways, form a network to prepare for the upregulation of Id2 and GATA-3, which together form the executive regulatory network to direct lineage fate determination of ILCs, possibly with continued assistance from the initiation transcription factors such as Tcf7, Tox, and Nfil3 (Figure 2). Additional experiments are required to confirm this proposed regulatory network model and it is likely that additional regulators for ILC development may soon be discovered.

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.