Role of 2B4 on dermal γδ T cells in the development of psoriasis-like skin inflammation

Abstract

Abstract Psoriasis is a chronic inflammatory skin disease that has comorbid with systemic inflammatory disease, however, their precise pathologic mechanisms remain poorly understood. Transcriptome analysis of dermis in the psoriasis patient has revealed that the signaling lymphocyte activation molecule (SLAM) family receptor, 2B4 (CD244), was significantly down-regulated in the skin of psoriasis patients, suggesting that 2B4 might have served as an important regulator in the process of psoriatic inflammation. To test this hypothesis, we induced psoriatic skin inflammation with topical application of Imiquimod (IMQ), a toll-like receptor 7 ligand, on the back skin of WT or 2B4KO mice and examined their clinical disease score up to 6 days. As expected, IMQ-treated WT mice exhibited the signs of erythema, scales and skin thickness, however all these clinical manifestations were significantly worsened in 2B4KO mice. Furthermore, 2B4 deficiency caused elevated expression of antimicrobial peptides, along with increased IL-17A, a key cytokine driving the pathogenesis of psoriasis. Upon further analysis, we found that increased IL-17A production in the psoriatic skin of 2B4KO mice was attributed to the presence of dermal γδ T cells, not DCs or monocytes, within inflamed skin. Taken together, we present a previously unidentified role of 2B4 as a key coreceptor regulating the pathogenesis of psoriasis via controlling the dermal γδ T cells.