Tissue resident memory T cells triggered recurrent psoriasiform dermatitis dependent on RELA/p52 signaling in mice

Abstract Immunological memory triggered recurrence is the critical challenge in treating psoriasis. Tissue resident memory T (Trm) cells is the primary pacemaker in recurrent psoriasiform dermatitis, but the mechanism of activating Trm cells is still unclear. In this study, imiquimod induced recurrent psoriatic mice were established to reveal the phenotype of different Trm cells. Then, CD8⁺/CD4⁺ Tcm cells injection and NF-κB inhibitor/agonist were used to investigate the role and mechanism of Trm in recurrent psoriasis. Mice displayed severe dermatitis, high PASI scores and inflammatory cytokines after repeated imiquimod treatment. The CD8⁺ Trm cells ,but not CD4⁺ Trm cells, were elevated in skin of recurrent psoriatic mice. The CD8⁺ Tcm cells injection elicited more severe psoriatic symptom than imiquimod treatment alone, which indicate CD8⁺ Trm cells is critical participant in psoriatic recurrence. Meanwhile, the phosphorylated of NF-κB p52 and NF-κB p65 (RELA) both were enhanced in skin of imiquimod induced recurrent psoriatic mice. On the contrary, NF-κB inhibitor/agonist significantly suppressed/restore the dermatitis and CD8⁺ Trm cells in recurrent psoriatic mice. Hence, canonical and non-canonical NF-κB signaling both may contribute to activate CD8⁺ Trm cells in recurrent psoriasis.