Double-negative T cells ameliorate psoriasis by selectively inhibition on IL-17A producing ?d T cells

Psoriasis is a chronic immune-mediated skin condition influenced by genetics and environmental factors. ?d T cells, as the main sources of IL-17A, play pivotal roles in the inflammatory processes of psoriasis. During psoriasis pathogenesis, inhibiting the secretion of IL-17A has emerged as a novel therapeutic approach for treating psoriasis. Double-negative T (DNT) cells is a novel type of immunosuppressive cells. Our preliminary research has unveiled that DNT cells play a significant immunoregulatory role in autoimmune and allergic diseases. In this study, we aimed to evaluate the protection of DNT cells and explore its underlying mechanism. Overall design: We conducted adoptive transfer of CD4 T cell converted DNT cells (cDNT) into the IMQ-induced psoriasis mouse model through tail vein injection. Following cDNT treatment, there was a reduction in the inflammatory response in mouse skin, characterized by decreased skin folds, scales, and red patches. After cDNT treatment, the secretion of IL-17A by RORc+ ?dlow T cells in the skin was suppressed, resulting in an amelioration of skin inflammation. Transcriptomic data suggested heightened expression of NKG2D ligands in ?dlow T cell within the mouse model of psoriasis induced by IMQ. When blocked NKG2D ligand and NKG2D (expressed by cDNT) interaction, the cytotoxic efficacy of cDNT against RORc+IL17A+ ?dlow T cells was attenuated. Using Ccr5-/- cDNT for treatment yielded evidence that cDNT migrate into the inflamed skin tissue, failed to pretocet IMQ induced skin lesion.