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Interleukin-1β-induced IRAK1 ubiquitination is required for TH-GM-CSF cell differentiation in T cell-mediated inflammation.
- Source :
-
Journal of Autoimmunity . Aug2019, Vol. 102, p50-64. 15p. - Publication Year :
- 2019
-
Abstract
- Accumulating evidence suggests granulocyte macrophage-colony stimulating factor (GM-CSF) can function as an inflammatory mediator, but whether GM-CSF-producing CD4+ T cells (T H -GM-CSF) are a distinct T helper cell subset is lacking. Herein we demonstrate that interleukin (IL)-1β exclusively drives differentiation of naïve CD4+ T cells into T H -GM-CSF cells via inducing ubiquitination of IL-1 receptor-associated kinase 1 (IRAK1) and subsequent activation of the transcription factor NF-kappaB (NF-κB), independent of RAR-related orphan receptor gamma (RORγt) required for T H 17 differentiation. In vivo, T H -GM-CSF cells are present in murine Citrobacter Rodentium infections and mediate colitis following adoptive transfer of CD4+ T cells into Rag1 −/− mice via GM-CSF-induced macrophage activation. The T H -GM-CSF cell phenotype is stable and distinct from the T H 17 genetic program, but IL-1β can convert pre-formed T H 17 cells into T H -GM-CSF cells, thereby accounting for previously reported associations between IL-17 and GM-CSF. Together, our results newly identify IL-1β/NF-κB-dependent T H -GM-CSF cells as a unique T helper cell subset and highlight the importance of CD4+ T cell-derived GM-CSF induced macrophage activation as a previously undescribed T cell effector mechanism. • Our study newly identifies GM-‐CSF-‐single producing T helper cells (TH-‐GM-‐CSF) as a unique T helper subset. • Our study reveals that IL-‐1® directly programs TH-‐GM-‐CSF differentiation via IRAK1/NF-‐κB axis and that IL-‐1® induces conversion of TH17 into TH-‐GM-‐CSF. • Our study shows that TH-‐GM-‐CSF cells are critically involved in the development of T cell transfer induced colitis. These novel findings will lead to more exciting investigations concerning the contributions of TH-‐GM-‐CSF in various T cell-‐ mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08968411
- Volume :
- 102
- Database :
- Academic Search Index
- Journal :
- Journal of Autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 137493714
- Full Text :
- https://doi.org/10.1016/j.jaut.2019.04.010