title: IL-22 exacerbates the severity of CVB3-induced acute viral myocarditis in IL-17A-deficient mice.
abstract: Interleukin (IL)-22 has either proinflammatory or tissue‑protective properties, depending on the nature of the affected tissue and the local cytokine milieu, including the presence or absence of IL-17A co-expression. We have previously demonstrated that IL-22 has critical anti-inflammatory and antiviral roles in mice with coxsackievirus B3 (CVB3)‑induced acute viral myocarditis (AVMC) in the presence of IL-17A. However, whether IL-17A determines the function of IL-22 in AVMC remains unknown. Therefore, the present study, in continuation of our previous investigations, aimed to determine whether IL-22 plays a distinctly different role in the absence of IL-17A in AVMC by using IL-17A-deficient mice. Results demonstrated that the neutralization of IL-22 in IL-17A‑deficient mice alleviated the severity of myocarditis. This was demonstrated by the lower pathological scores of heart sections and ratios of heart weight/body weight (HW/BW), reduced production of activator of transcription 3 (STAT3) and proinflammatory cytokines TNF-α and IL-6, followed by increased viral replication and decreased levels of the antiviral cytokine IFN-γ. Furthermore, the correlation between cardiac CVB3 RNA and IL-22 mRNA or IFN-γ mRNA was negative. In conclusion, IL-22 exacerbated the severity of AVMC and restrained viral replication in the absence of IL-17A. Spleen lymphocytes cultured with recombinant IL-17 (rIL-17) increased the production of IL-22. Combined with our previous data, these results indicate that IL-17A is not involved in regulating the antiviral role, however, may mediate the tissue-protective versus pathogenic properties of IL-22 in CVB3-induced AVMC in mice.
authors: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning, Guangxi 530021, P.R. China.
authors: Qing
authors: Q
authors: Kong
authors: Yimin
authors: Y
authors: Xue
authors: Weifeng
authors: W
authors: Wu
authors: Fan
authors: F
authors: Yang
authors: Yanli
authors: Y
authors: Liu
authors: Mengsha
authors: M
authors: Gao
authors: Wenyin
authors: W
authors: Lai
authors: Xiaofen
authors: X
authors: Pan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000235:genetics* / Q000472:pathogenicity; D006321:Heart / Q000503:physiopathology / Q000821:virology; D006801:Humans; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009205:Myocarditis / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D014779:Virus Replication / Q000235:genetics; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22