| First Author | Szilveszter KP | Year | 2021 |
| Journal | J Invest Dermatol | PubMed ID | 34656615 |
| Mgi Jnum | J:315198 | Mgi Id | MGI:6830876 |
| Doi | 10.1016/j.jid.2021.09.019 | Citation | Szilveszter KP, et al. (2021) Phospholipase Cgamma2 is Essential for Experimental Models of Epidermolysis Bullosa Acquisita. J Invest Dermatol |
| abstractText | Phospholipase Cgamma2 (PLCgamma2) mediates tyrosine kinasecoupled receptor signaling in various hematopoietic lineages. Although PLCgamma2 has been implicated in certain human and mouse inflammatory disorders, its contribution to autoimmune and inflammatory skin diseases is poorly understood. In this study, we tested the role of PLCgamma2 in a mouse model of epidermolysis bullosa acquisita triggered by antibodies against type VII collagen (C7), a component of the dermo-epidermal junction. PLCgamma2-deficient (Plcg2(-/-)) mice and bone marrow chimeras with a Plcg2(-/-) hematopoietic system were completely protected from signs of anti-C7-induced skin disease, including skin erosions, dermalepidermal separation, and inflammation, despite normal circulating levels and skin deposition of anti-C7 antibodies. PLCgamma2 was required for the tissue infiltration of neutrophils, eosinophils, and monocytes/macrophages as well as for the accumulation of proinflammatory mediators (including IL-1beta, MIP-2, and LTB4) and reactive oxygen species. Mechanistic experiments revealed a role for PLCgamma2 in the release of proinflammatory mediators and reactive oxygen species but not in the intrinsic migratory capacity of leukocytes. The phospholipase C inhibitor U73122 inhibited dermal-epidermal separation of human skin sections incubated with human neutrophils in the presence of anti-C7 antibodies. Taken together, our results suggest a critical role for PLCgamma2 in the pathogenesis of the inflammatory form of epidermolysis bullosa acquisita. |
