TLR2 Deficiency Exacerbates Imiquimod-Induced Psoriasis-Like Skin Inflammation through Decrease in Regulatory T Cells and Impaired IL-10 Production
| Autor: | Sohshi Morimura, Makoto Sugaya, Shinichi Sato, Yoshihide Asano, Hideki Fujita, Momoko Nakao, Tomomitsu Miyagaki, Sayaka Shibata |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Inflammation chemical and pharmacologic phenomena T-Lymphocytes Regulatory Article Catalysis regulatory T cells Proinflammatory cytokine lcsh:Chemistry Inorganic Chemistry Mice 03 medical and health sciences 0302 clinical medicine Immune system Psoriasis medicine Animals TLR2 dendritic cells Physical and Theoretical Chemistry Receptor lcsh:QH301-705.5 Molecular Biology Spectroscopy Skin Mice Knockout business.industry Organic Chemistry General Medicine psoriasis medicine.disease Toll-Like Receptor 2 Interleukin-10 Computer Science Applications imiquimod Interleukin 10 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Immunology medicine.symptom business 030215 immunology |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 22 International Journal of Molecular Sciences, Vol 21, Iss 8560, p 8560 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21228560 |
| Popis: | Emerging evidence has demonstrated that Toll-like receptors (TLRs) are associated with autoimmune diseases. In this study, we investigated the role of TLR2 in psoriasis using imiquimod-induced psoriasis-like dermatitis. Although TLR2 signaling is known to play a critical role in the induction of proinflammatory cytokines by immune cells, such as dendritic cells (DCs), macrophages, and monocytes, TLR2 deficiency unexpectedly exacerbated psoriasiform skin inflammation. Importantly, messenger RNA (mRNA) levels of Foxp-3 and IL-10 in the lesional skin were significantly decreased in TLR2 KO mice compared with wild-type mice. Furthermore, flow cytometric analysis of the lymph nodes revealed that the frequency of regulatory T cells (Tregs) among CD4-positive cells was decreased. Notably, stimulation with Pam3CSK4 (TLR2/1 ligand) or Pam2CSK4 (TLR2/6 ligand) increased IL-10 production from Tregs and DCs and the proliferation of Tregs. Finally, adoptive transfer of Tregs from wild-type mice reduced imiquimod-induced skin inflammation in TLR2 KO mice. Taken together, our results suggest that TLR2 signaling directly enhances Treg proliferation and IL-10 production by Tregs and DCs, suppressing imiquimod-induced psoriasis-like skin inflammation. Enhancement of TLR2 signaling may be a new therapeutic strategy for psoriasis. |
| Databáze: | OpenAIRE |
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