Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORγt induction as downstream targets of Stat3

Tanaka, Shigeru; Suto, Akira; Iwamoto, Taro; Kashiwakuma, Daisuke; Kagami, Shin-ichiro; Suzuki, Kotaro; Takatori, Hiroaki; Tamachi, Tomohiro; Hirose, Koichi; Onodera, Atsushi; Suzuki, Junpei; Ohara, Osamu; Yamashita, Masakatsu; Nakayama, Toshinori; Nakajima, Hiroshi

doi:10.1084/jem.20130791

Cited by 112 publications

(122 citation statements)

References 52 publications

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“…Notably, CD4 + Ki67 + cells recovered from c-Maf KO-T immunized mice expressed higher levels of T-bet or GATA-3, the major transcription factors associated with the Th1- or Th2-cell differentiation program, respectively (Figures 4H,I,L–O). As expected from the literature (21), c-Maf KO-T mice failed to express optimal levels of RORγt following immunization (Figures 4G,K).…”

Section: Resultssupporting

confidence: 88%

The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells

et al. 2017

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Follicular helper T cells (Tfh) have been identified as the primary cell subpopulation regulating B cell responses in germinal centers, thus supporting high-affinity antibody production. Among the transcription factors orchestrating Tfh cell differentiation and function, the role played by the proto-oncogene c-Maf remains poorly characterized. We report herein that selective loss of c-Maf expression in the T cell compartment results in defective development of Tfh cells in response to both antigen/adjuvant vaccinations and commensal intestinal bacteria. Accordingly, c-Maf expression in T cells was essential for the development and high-affinity antibody secretion in vaccinated animals. c-Maf was expressed early, concomitantly to BCL6, in Tfh cell precursors and found to regulate Tfh fate in a cell-autonomous fashion. Altogether, our findings reveal a novel, non-redundant, function for c-Maf in the differentiation of Tfh cells and the regulation of humoral immune responses to T-cell-dependent antigens.

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Section: Resultssupporting

confidence: 88%

The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells

et al. 2017

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“…However, Blk deficiency has been shown to result in failure to generate IL-17-producing γδ T cells 26 , which would suggest that Blk might have a similar role in i NKT cells. The TFs SOX5 and c-MAF have been shown to work together to stimulate Rorc expression in CD4 + T H 17 cells 27 , and the related SOXD-group protein SOX13 is required for the differentiation of IL-17-producing γδ T cells 28 . Notably, expression of Maf and Sox13 transcripts (Fig.…”

Section: Resultsmentioning

confidence: 99%

Innate-like functions of natural killer T cell subsets result from highly divergent gene programs

et al. 2016

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Natural killer T cells (NKT cells) have stimulatory or inhibitory effects on the immune response that can be attributed in part to the existence of functional subsets of NKT cells. These subsets have been characterized only on the basis of the differential expression of a few transcription factors and cell-surface molecules. Here we have analyzed purified populations of thymic NKT cell subsets at both the transcriptomic level and epigenomic level and by single-cell RNA sequencing. Our data indicated that despite their similar antigen specificity, the functional NKT cell subsets were highly divergent populations with many gene-expression and epigenetic differences. Therefore, the thymus ‘imprints’ distinct gene programs on subsets of innate-like NKT cells that probably impart differences in proliferative capacity, homing, and effector functions.

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“…Indeed, ICOS priming induces, to a greater extent than CD28, genes implicated in bolstering Th17 fate. First, ICOS increased the expression of RORC (Figure 2A), a master transcription factor for Th17 cell differentiation (5). We confirmed enhanced RORγt expression by flow cytometry ( Figure 2B).…”

Section: Icos Signaling Augments Antitumor Th17 Cell Immunitysupporting

confidence: 57%

β-catenin and PI3Kδ inhibition expands precursor Th17 cells with heightened stemness and antitumor activity

Majchrzak¹,

Nelson²,

Bowers³

et al. 2017

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Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORγt induction as downstream targets of Stat3

Abstract: A novel isoform of Sox5, Sox5t, and c-Maf activate RORγt to induce Th17 cells. Sox5−/− mice exhibit impaired Th17 differentiation and are thus resistant to EAE and delayed-type hypersensitivity.

Cited by 112 publications

References 52 publications

The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells

The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells

Innate-like functions of natural killer T cell subsets result from highly divergent gene programs

β-catenin and PI3Kδ inhibition expands precursor Th17 cells with heightened stemness and antitumor activity

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