In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 142.23-142.23
Abstract:
CD4+ T cells, especially Th17 cells, are instrumental in the development and progression of autoimmune diseases, such as multiple sclerosis (MS), psoriasis, and rheumatoid arthritis. While pathogenic Th17 cells drive inflammation in autoimmunity, the molecular programming underlying their pathogenicity remains insufficiently understood. Furthermore, very little is known regarding the role of the pattern recognition receptor TLR2 in Th17 pathogenicity. We have previously shown that activation of TLR2 with PAM3CSK4 during Th17 differentiation results in increased production of IL-17A and IL-17F and significantly increases the proliferation of Th17 cells in vitro. Herein, we show that TLR2 induces pathogenicity in Th17 cells, similar to what has been shown for IL-23. TLR2 signaling results in increased encephalitogenic migration of Th17 cells, in addition to increased cytokine production. To further investigate the effect of TLR2 activation on Th17 cells, we utilized RNA sequencing and found 390 genes that are upregulated and 355 genes that are downregulated following TLR2 signaling in Th17 cells. Several of these genes we have identified are important regulators that either increase or restrain the inflammatory potential of Th17 cells. We further address the role of TLR2 in Th17-mediated autoimmune disease using experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We show that encephalitogenic Th17 cells expanded with a TLR2 agonist induced EAE disease to the same extent as those expanded with IL-23. Altogether, this study establishes TLR2 signaling as crucial for induction of pathogenic Th17 cells in autoimmune disease.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.204.Supp.142.23
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2020
detail.hit.zdb_id:
1475085-5
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