IL-1 signaling is critical for expansion but not generation of autoreactive GM-CSF+ Th17 cells.
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.
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany ilgiz.mufazalov@uni-mainz.de waisman@uni-mainz.de.
Ilgiz A
0000-0001-9332-0131
IA
Mufazalov
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Carsten
C
Schelmbauer
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Tommy
T
Regen
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Janina
J
Kuschmann
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Florian
F
Wanke
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Laureen A
LA
Gabriel
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Judith
J
Hauptmann
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Werner
0000-0002-1297-9725
W
Müller
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Emmanuel
E
Pinteaux
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Florian C
FC
Kurschus
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany ilgiz.mufazalov@uni-mainz.de waisman@uni-mainz.de.
Ari
0000-0003-4304-8234
A
Waisman
D000818:Animals; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis*; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D037342:Pertussis Toxin / Q000008:administration & dosage / Q000633:toxicity; D058504:Th17 Cells / Q000737:chemistry* / Q000502:physiology*
D007375:Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D037342:Pertussis Toxin
EAE; GM‐CSF; IL‐1; Th17; autoimmunity