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IL-12 signaling drives the differentiation and function of a T H 1-derived T FH1 -like cell population.
- Source :
-
Scientific reports [Sci Rep] 2019 Sep 30; Vol. 9 (1), pp. 13991. Date of Electronic Publication: 2019 Sep 30. - Publication Year :
- 2019
-
Abstract
- CD4 <superscript>+</superscript> T follicular helper (T <subscript>FH</subscript> ) cells provide help to B cells and promote antibody-mediated immune responses. Increasing evidence supports the existence of T <subscript>FH</subscript> populations that secrete cytokines typically associated with the effector functions of other CD4 <superscript>+</superscript> T cell subsets. These include T helper 1 (T <subscript>H</subscript> 1)-biased T <subscript>FH</subscript> (T <subscript>FH1</subscript> ) cells that have recognized roles in both immune responses to pathogens and also the pathogenesis of autoimmune disease. Given their apparent importance to human health, there is interest in understanding the mechanisms that regulate T <subscript>FH1</subscript> cell formation and function. However, their origin and the molecular requirements for their differentiation are unclear. Here, we describe a population of murine T <subscript>H</subscript> 1-derived, T <subscript>FH1</subscript> -like cells that express the chemokine receptor Cxcr3 and produce both the T <subscript>H</subscript> 1 cytokine interferon-γ and the T <subscript>FH</subscript> -associated cytokine interleukin-21 (IL-21). Furthermore, these T <subscript>FH1</subscript> -like cells promote B cell activation and antibody production at levels indistinguishable from conventional IL-6-derived T <subscript>FH</subscript> -like cells. Regarding their regulatory requirements, we find that IL-12 signaling is necessary for the differentiation and function of this T <subscript>FH1</subscript> -like cell population. Specifically, IL-12-dependent activation of STAT4, and unexpectedly STAT3, promotes increased expression of IL-21 and the T <subscript>FH</subscript> lineage-defining transcription factor Bcl-6 in T <subscript>FH1</subscript> -like cells. Taken together, these findings provide insight into the potential origin and differentiation requirements of T <subscript>FH1</subscript> cells.
- Subjects :
- Animals
Cell Differentiation
Flow Cytometry
Gene Expression Regulation
Interferon-gamma metabolism
Interleukin-12 physiology
Interleukins metabolism
Mice
Mice, Inbred C57BL
Polymerase Chain Reaction
STAT3 Transcription Factor metabolism
STAT4 Transcription Factor metabolism
Th1 Cells metabolism
Interleukin-12 metabolism
Signal Transduction
Th1 Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 31570752
- Full Text :
- https://doi.org/10.1038/s41598-019-50614-1