Potential role of IL-37 signaling pathway in feedback regulation of autoimmune Hashimoto thyroiditis
- 112 Downloads
IL-37, the anti-inflammatory cytokine of the IL-1 family, plays several key roles in the regulation of autoimmune diseases. Yet, its role in Hashimoto’s thyroiditis (HT) is not clear. In the present study, we found that, in tissues from HT patients, most of the follicular epithelial cells were positive for both IL-37 and single Ig IL-1-related receptor (SIGIRR) by immunohistochemical staining, while the infiltrating lymphocytes and other inflammatory cells hardly expressed any. Meanwhile, mRNA expression levels of IL-37 in peripheral blood mononuclear cells (PBMC) of HT patients were significantly higher than those in normal controls measured by quantitative real-time PCR. Finally, we studied the possible role of IL-37 in IFN-γ-stimulated rat FRTL-5 cells. The results showed that IL-1β, TNF-α, and MCP-1 mRNA levels were significantly decreased, while the expression of IL-4 mRNA was dramatically up-regulated in IFN-γ-stimulated rat thyroid cell line FRTL-5 pre-treated with IL-37. The current study, for the first time, demonstrated that the IL-37 network is involved in Hashimoto’s thyroiditis, and IL-37 signaling pathway may ameliorate the excessive autoimmune responses in this chronic lymphocytic thyroiditis.
KeywordsHashimoto’s thyroiditis Chronic lymphocytic thyroiditis IL-37 SIGIRR
This study was supported by two grants from the National Natural Science Foundation of China (81802027 and 81271864) and a grant from Anhui Provincial National Science Foundation (1608085MH173).
- Luo Y, Cai X, Liu S, Wang S, Nold-Petry CA, Nold MF, Bufler P, Norris D, Dinarello CA, Fujita M (2014) Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells. Proc Natl Acad Sci USA 111:15178–15183. https://doi.org/10.1073/pnas.1416714111 CrossRefPubMedGoogle Scholar
- Moretti S, Bozza S, Oikonomou V, Renga G, Casagrande A, Iannitti RG, Puccetti M, Garlanda C, Kim S, Li S et al (2014) IL-37 inhibits inflammasome activation and disease severity in murine aspergillosis. PLoS Pathog 10:e1004462. https://doi.org/10.1371/journal.ppat.1004462 CrossRefPubMedCentralGoogle Scholar
- Nold-Petry CA, Lo CY, Rudloff I, Elgass KD, Li S, Gantier MP, Lotz-Havla AS, Gersting SW, Cho SX, Lao JC et al (2015) IL-37 requires the receptors IL-18Ralpha and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol 16:354–365. https://doi.org/10.1038/ni.3103 CrossRefPubMedGoogle Scholar
- Riva F, Bonavita E, Barbati E, Muzio M, Mantovani A, Garlanda C (2012) TIR8/SIGIRR is an interleukin-1 receptor/Toll like receptor family member with regulatory functions in inflammation and immunity. Front Immunol 3:322. https://doi.org/10.3389/fimmu.2012.00322 CrossRefPubMedPubMedCentralGoogle Scholar
- Ruggeri RM, Cristani M, Vicchio TM, Alibrandi A, Giovinazzo S, Saija A, Campenni A, Trimarchi F, Gangemi S (2019) Increased serum interleukin-37 (IL-37) levels correlate with oxidative stress parameters in Hashimoto’s thyroiditis. J Endocrinol Invest 42:199–205. https://doi.org/10.1007/s40618-018-0903-3 CrossRefGoogle Scholar
- Santaguida MG, Nardo S, Del Duca SC, Lococo E, Virili C, Gargano L, Lenti L, Centanni M (2011) Increased interleukin-4-positive lymphocytes in patients with Hashimoto’s thyroiditis and concurrent non-endocrine autoimmune disorders. Clin Exp Immunol 165:148–154. https://doi.org/10.1111/j.1365-2249.2011.04419.x CrossRefPubMedPubMedCentralGoogle Scholar
- Szabo-Fresnais N, Blondeau JP, Pomerance M (2008) Activation of the cAMP pathway synergistically increases IL-1-induced IL-6 gene expression in FRTL-5 thyroid cells: involvement of AP-1 transcription factors. Mol Cell Endocrinol 284:28–37. https://doi.org/10.1016/j.mce.2007.12.017 CrossRefPubMedGoogle Scholar
- Ye L, Ji L, Wen Z, Zhou Y, Hu D, Li Y, Yu T, Chen B, Zhang J, Ding L et al (2014) IL-37 inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells of patients with systemic lupus erythematosus: its correlation with disease activity. J Transl Med 12:69. https://doi.org/10.1186/1479-5876-12-69 CrossRefPubMedPubMedCentralGoogle Scholar