Costimulatory molecule ICOS plays a critical role in the development of TH-17 and follicular T-helper cells by regulating c-Maf expression and IL-21 production

By Aurelie T Bauquet, Hulin Jin, A. Paterson, M. Mitsdoerffer, I. Ho, Arlene H. Sharpe, V. Kuchroo. Nature Immunology, 2008

746 citations recorded by the source corpus.

The inducible costimulatory molecule ICOS has been suggested to be important in the development of interleukin 17 (IL-17)-producing helper T cells (TH-17 cells) and of follicular helper T cells (TFH cells). Here we show that ICOS-deficient mice had no defect in TH-17 differentiation but had fewer TH-17 cells after IL-23 stimulation and fewer TFH cells. We also show that TFH cells produced IL-17 and that TFH cells in ICOS-deficient mice were defective in IL-17 production. Both TH-17 and TFH cells had higher expression of the transcription factor c-Maf. Genetic loss of c-Maf resulted in a defect in IL-21 production and fewer TH-17 and TFH cells. Thus our data suggest that ICOS-induced c-Maf regulates IL-21 production that in turn regulates the expansion of TH-17 and TFH cells.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/a51a99f6590937d00ff0b04716241ffb3ae73979

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In Immunology

1. Shane Crotty
2. Jinfang Zhu
3. W. E. Paul
4. J. O’Shea
5. Jacques Banchereau
6. V. Kuchroo
7. V. Pascual
8. F. Quintana

Citations in the corpus

• Follicular Helper T Cells. (2016, background): “The absence of c-MAF reduces the number of Th2, Th17, and Tfh cells (68).”
• Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion (2011, background): “Consistent with previous studies with Tfh cells (Bauquet et al., 2009; Odegard et al., 2008; Vogelzang et al., 2008), B cell help by blood CXCR5+CD4+ T cells was also depen- dent on ICOS, as shown by the fact that blocking of ICOS-ICOS ligand interaction inhibited both IL-21 secretion (Figure S2B)…”
• Bcl6 dependent T follicular helper cell differentiation diverges from effector cell differentiation during priming and depends on the gene Icos (2011, positive): “Several studies have shown that Tfh cells can exhibit features of Th1, Th2, and Th17 cells (Bauquet et al., 2009; Fazilleau et al., 2009; Johnston et al., 2009; Reinhardt et al., 2009; Zaretsky et al., 2009).”
• Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. (2011, neutral): “, 2009), Stat3, c-Maf (Bauquet et al., 2009), AHR (Veldhoen et al.”
• IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses (2010, background): “Within the CD4+ T cell subset, IL-21 is expressed at the highest levels by T follicular helper (Tfh) cells and Th17 cells (Chtanova et al., 2004; Nurieva et al., 2007; Bauquet et al., 2009).”
• The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. (2009, background): “Recent data has shown that IL-21 is regulated by c-Maf, a transcription factor also expressed by Th2, Th17, and Tfh cells (Bauquet et al., 2009; Pot et al., 2009).”
• Interleukin-22: immunobiology and pathology (2015, background): “ICOS Negative Induction of c-Maf and reduced expression of IL-22 (227, 228)”
• Differentiation of Effector CD4 T Cell Populations (2010, positive): “Recently, c-Maf has been found to be highly expressed in Tfh cells that are capable of producing IL-17, and IL-17-producing Tfh cells are less frequent in Maf knockout mice (167).”
• Treg cells expressing the co-inhibitory molecule TIGIT selectively inhibit pro-inflammatory Th1 and Th17 cell responses (2014, background): “Simi- larly, inducible costimulator (ICOS) regulates T follicular helper (Tfh) cell expansion and critically contributes to Th17 cell func- tion by regulating IL-23 receptor expression in an IL-21- and c-Maf-dependent manner (Bauquet et al., 2009).”