TLR7 signaling regulates Th17 cells and autoimmunity: Novel potential for autoimmune therapy

Jian Ye, Yadan Wang, Xia Liu, Lingyun Li, Adeleye Opejin, Eddy C. Hsueh, Huanle Luo, Tian Wang, Daniel Hawiger, Guangyong Peng

Research output: Contribution to journalArticle

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Abstract

Innate regulation through TLR signaling has been shown to be important for promoting T cell subset development and function. However, limited information is known about whether differential TLR signaling can selectively inhibit Th17 and/or Th1 cells, which are important for controlling excessive inflammation and autoimmune responses. In this article, we demonstrate that activation of TLR7 signaling in T cells can inhibit Th17 cell differentiation from naive T cells and IL-17 production in established Th17 cells. We further report that downregulation of STAT3 signaling is responsible for TLR7-mediated inhibition of Th17 cells due to induction of suppressor of cytokine signaling 3 and 5. TLR7-mediated suppression of Th17 cells does not require dendritic cell involvement. In addition, we show that TLR7 signaling can suppress Th1 cell development and function through a mechanism different from Th17 cell suppression. Importantly, our complementary in vivo studies demonstrate that treatment with the TLR7 ligand imiquimod can inhibit Th1 and Th17 cells, resulting in the prevention of, and an immunotherapeutic reduction in, experimental autoimmune encephalomyelitis. These studies identify a new strategy to manipulate Th17/Th1 cells through TLR7 signaling, with important implications for successful immunotherapy against autoimmune and inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)941-954
Number of pages14
JournalJournal of Immunology
Volume199
Issue number3
DOIs
StatePublished - Aug 1 2017

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Th17 Cells
Autoimmunity
Th1 Cells
Therapeutics
imiquimod
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Interleukin-17
T-Lymphocyte Subsets
Immunotherapy
Dendritic Cells
Autoimmune Diseases
Cell Differentiation
Down-Regulation
Cytokines
Ligands
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Ye, J., Wang, Y., Liu, X., Li, L., Opejin, A., Hsueh, E. C., ... Peng, G. (2017). TLR7 signaling regulates Th17 cells and autoimmunity: Novel potential for autoimmune therapy. Journal of Immunology, 199(3), 941-954. https://doi.org/10.4049/jimmunol.1601890

TLR7 signaling regulates Th17 cells and autoimmunity : Novel potential for autoimmune therapy. / Ye, Jian; Wang, Yadan; Liu, Xia; Li, Lingyun; Opejin, Adeleye; Hsueh, Eddy C.; Luo, Huanle; Wang, Tian; Hawiger, Daniel; Peng, Guangyong.

In: Journal of Immunology, Vol. 199, No. 3, 01.08.2017, p. 941-954.

Research output: Contribution to journalArticle

Ye, J, Wang, Y, Liu, X, Li, L, Opejin, A, Hsueh, EC, Luo, H, Wang, T, Hawiger, D & Peng, G 2017, 'TLR7 signaling regulates Th17 cells and autoimmunity: Novel potential for autoimmune therapy', Journal of Immunology, vol. 199, no. 3, pp. 941-954. https://doi.org/10.4049/jimmunol.1601890
Ye, Jian ; Wang, Yadan ; Liu, Xia ; Li, Lingyun ; Opejin, Adeleye ; Hsueh, Eddy C. ; Luo, Huanle ; Wang, Tian ; Hawiger, Daniel ; Peng, Guangyong. / TLR7 signaling regulates Th17 cells and autoimmunity : Novel potential for autoimmune therapy. In: Journal of Immunology. 2017 ; Vol. 199, No. 3. pp. 941-954.
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