Phospholipase Cγ2 (PLCγ2) is an important member of immunoreceptor signaling, expressed mostly in haemopoietic cells. Gain-of-function mutations of PLCγ2 have been reported in both mice and human cases causing a complex syndrome involving skin manifestations resembling epidermolysis bullosa. Previously we showed that PLCγ2 deficient mice remained protected in an autoimmune dermatitis model induced by the passive transfer of autoantibodies against collagen type VII (anti-C7), which is a key anchoring fibril in the dermal-epidermal junction. Our aim was to further characterize the mechanisms leading to this phenotype in PLCγ2 deficient mice.
Anti-C7 antibody level in blood was tested by ELISA. Histology samples were made followed by H&E and immunostaining. Leukocyte accumulation in ear samples was measured by flow cytometry. Generation of proinflammatory microenvironment in the skin was analysed by ELISA.
Anti-C7 IgG was present in the circulation and showed deposition along the dermal-epidermal junction in both genotypes. According to histology and flow cytometry a severe dermal immune cell infiltration, mostly neutrophil accumulation developed in wild type mice with the increase of proinflammatory mediators in the inflamed skin. However, neutrophil infiltration and production of proinflammatory mediators were abrogated in PLCγ2 deficient animals.
Taken together, PLCγ2 deficient mice were completely protected from skin inflammation upon anti-C7 treatment. Neutrophil accumulation and the proinflammatory microenvironment failed to develop in the skin in the absence of PLCγ2. These results indicate that PLCγ2 has an essential role creating the proinflammatory milieu after autoantibody deposition in the skin.

Characterizing the Role of PLCγ2 in Autoantibody-induced Skin Inflammation