心肌炎症损伤的迁延不愈会导致心肌纤维化进而发展为DCM。因此，阐明心肌炎症损伤转归的机制对于预防该病的进展具有重要意义。预实验显示EAM小鼠脾脏和心肌组织NKp46+ILC3增加,产生IL-22；reHMGB1分泌上调；体内中和HMGB1能减少淋巴细胞浸润，缓解心肌纤维化；IL-22体外可抑制成纤维细胞胶原表达。有鉴于此，提出“reHMGB1促进NKp46+ILC3源性IL-22分泌,调节心肌纤维化”的假说。为证实这一假说，体外分别阐明reHMGB1对NKp46+ILC3活化、扩增、IL-22分泌影响；IL-22体外抑制IL-17、TGF-β诱导的心肌胶原表达的机制；体内使用WT、IL-22-/-、IL-22BP-/-小鼠诱导EAM，并使用reHMGB1、rIL-22BP、抗HMGB1和抗CD90.2抗体进行干预，进一步证实上述假说。通过以上研究有望阐明心肌炎症损伤转归与心功能重塑的机制。

The chronic inflammation will lead to cardiac fibrosis and then progress into dilated cardiomyopathy (DCM). Therefore, it is of great significance to elucidate the mechanism of cardiac inflammatory resolution for prevention the progress of myocarditis. Our data showed that the IL-22 producing NKp46+ILC3 cells were expanded and reduced HMGB1 (reHMGB1) was up-regulated in the spleen and myocardium of EAM mice. HMGB1 blockade could significantly decrease the lymphocytes infiltration and ameliorate fibrosis. IL-22 could inhibit collagen expression in fibroblasts in vitro. In view of this, we speculate that "IL-22 producing NKp46+ILC3 cells expansion induced by reHMGB1 regulates cardiac fibrosis". To confirm this hypothesis, in vitro, firstly, the mechanism of reHMGB1 promoting activation and expansion of NKp46+ILC3 will be demonstrated. Secondly, how does IL-22 inhibit IL-17 and TGF-β induced collagen expression? In vivo, wild type, IL-22 deficient and IL-22BP deficient mice will be used to induce EAM model. Recombinant HMGB1 (rHMGB1), rIL-22BP, anti-HMGB1 antibody and anti-CD90.2 antibody will be used, respectively, as the intervention factors to further confirm the above hypothesis. The inflammatory resolving and cardiac remodeling mechanisms of cardiac injury will be clearly demonstrated by the present project.