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IL-7/IL-7 Receptor Signaling Differentially Affects Effector CD4+ T Cell Subsets Involved in Experimental Autoimmune Encephalomyelitis.


ABSTRACT: IL-17-producing CD4(+) T (Th17) cells, along with IFN-?-expressing Th1 cells, represent two major pathogenic T cell subsets in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). The cytokines and transcription factors involved in the development and effector functions of Th1 and Th17 cells have been largely characterized. Among them, IL-23 is essential for the generation of stable and encephalitogenic Th17 cells and for the development of EAE. The IL-7/IL-7R signaling axis participates in cell survival, and perturbation of this pathway has been associated with enhanced susceptibility to MS. A link between IL-23-driven pathogenic T cells and IL-7/IL-7R signaling has previously been proposed, but has not been formally addressed. In the current study, we showed that Th17 cells from mice with EAE express high levels of IL-7R? compared with Th1 cells. Using mice that constitutively express IL-7R? on T cells, we determined that sustained IL-7R expression in IL-23R-deficient mice could not drive pathogenic T cells and the development of EAE. IL-7 inhibited the differentiation of Th17 cells, but promoted IFN-? and GM-CSF secretion in vitro. In vivo IL-7/anti-IL-7 mAb complexes selectively expanded and enhanced the proliferation of CXCR3-expressing Th1 cells, but did not impact Th17 cells and EAE development in wild-type and IL-23R-deficient mice. Importantly, high IL-7 expression was detected in the CNS during EAE and could drive the plasticity of Th17 cells to IFN-?-producing T cells. Together, these data address the contribution of IL-23/IL-23R and IL-7/IL-7R signaling in Th17 and Th1 cell dynamics during CNS autoimmunity.

SUBMITTER: Arbelaez CA 

PROVIDER: S-EPMC4546887 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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IL-7/IL-7 Receptor Signaling Differentially Affects Effector CD4+ T Cell Subsets Involved in Experimental Autoimmune Encephalomyelitis.

Arbelaez Carlos A CA   Glatigny Simon S   Duhen Rebekka R   Eberl Gerard G   Oukka Mohamed M   Bettelli Estelle E  

Journal of immunology (Baltimore, Md. : 1950) 20150729 5


IL-17-producing CD4(+) T (Th17) cells, along with IFN-γ-expressing Th1 cells, represent two major pathogenic T cell subsets in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). The cytokines and transcription factors involved in the development and effector functions of Th1 and Th17 cells have been largely characterized. Among them, IL-23 is essential for the generation of stable and encephalitogenic Th17 cells and for the development of EAE. The IL-7/  ...[more]

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