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

Psoriasis is a chronic immune-mediated skin condition influenced by genetics and environmental factors. γδ 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. 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+ γδlow T cells in the skin was suppressed, resulting in an amelioration of skin inflammation. Transcriptomic data suggested heightened expression of NKG2D ligands in γδlow 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+ γδlow 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.