PhD Scientific Days 2021

MO_I_L: Molecular Sciences I. Lectures

Characterizing the Role of PLCγ2 in Autoantibody-induced Skin Blistering

Text of the abstract

Phospholipase Cγ2 (PLCγ2) is a signaling molecule of tyrosine kinase-coupled receptors in cells of hematopoietic origin. Gain of-function mutations of PLCγ2 have been reported to cause a complex syndrome involving inflammation and bullous skin eruptions in both mice and humans.
Our aim was to test the role of PLCγ2 in autoantibody-induced skin blistering.
Skin blistering disease was triggered in wild type and PLCγ2-deficient mice by autoantibodies against type VII collagen (C7), a component of the dermal-epidermal junction. Disease course was followed by scoring and histology. Leukocyte accumulation was measured by flow cytometry. Migrating capacity of myeloid cells was checked both in vitro and in an in vivo competitive migration assay. Autoantibody deposition and the generation of the proinflammatory microenvironment in the skin was analyzed by ELISA and in vivo luminescence-based imaging. In vitro neutrophil activation was examined on immobilized C7-
anti-C7 immune complex surfaces.
PLCγ2-deficient mice were completely protected from all clinical and microscopic signs of autoantibody-induced skin blistering. PLCγ2 deficiency prevented the infiltration of neutrophils, eosinophils and monocytes/macrophages to the ear tissue, however
the intrinsic migrating capacity of these cells and autoantibody deposition were not affected. The accumulation of various proinflammatory mediators and production of reactive oxygen species were completely blocked both in vitro and in vivo in the absence of PLCγ2.
Taken together, our results identify PLCγ2 as a critical component of autoantibody-induced skin blistering by creating a proinflammatory milieu after autoantibody deposition in the skin.

Funding: EFOP-3.6.3-VEKOP-16-2017-00009, Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine