IL-1 Signaling is Critical for Expansion but Not Generation of Autoreactive GM-CSF+ Th17 Cells

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2016 Nov 10

PMID 27827809

Citations 33

Authors

Ilgiz A Mufazalov

Carsten Schelmbauer

Tommy Regen

Janina Kuschmann

Florian Wanke

Laureen A Gabriel

Judith Hauptmann

Werner Muller

Emmanuel Pinteaux

Florian C Kurschus

Ari Waisman

Affiliations

Soon will be listed here.

Abstract

Interleukin-1 (IL-1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which IL-1 is involved in the generation of pathogenic T cells and in disease development remains largely unknown. We found that following EAE induction, pertussis toxin administration leads to IL-1 receptor type 1 (IL-1R1)-dependent IL-1β expression by myeloid cells in the draining lymph nodes. This myeloid-derived IL-1β did not vitally contribute to the generation and plasticity of Th17 cells, but rather promoted the expansion of a GM-CSF Th17 cell subset, thereby enhancing its encephalitogenic potential. Lack of expansion of GM-CSF-producing Th17 cells led to ameliorated disease in mice deficient for IL-1R1 specifically in T cells. Importantly, pathogenicity of IL-1R1-deficient T cells was fully restored by IL-23 polarization and expansion in vitro Therefore, our data demonstrate that IL-1 functions as a mitogenic mediator of encephalitogenic Th17 cells rather than qualitative inducer of their generation.

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