Allergin-1 inhibits TLR2-mediated mast cell activation and suppresses dermatitis

<span class="paragraphSection"><div class="boxTitle">Abstract</div>TLR2 recognizes cell wall components of <span style="font-style:italic;">Staphylococcus aureus</span>, which colonizes >90% of atopic eczematous skin lesions. The regulatory mechanisms of TLR2 signaling in the skin remain unclear. Allergin-1, an inhibitory immunoglobulin-like receptor containing an ITIM, is expressed on mast cells (MCs) and inhibits IgE-mediated anaphylaxis in mice. Here, we show that Allergin-1 inhibits TLR2-mediated activation of, and inflammatory cytokine production by, MCs <span style="font-style:italic;">in vitro</span>. Compared with wild-type mice, Allergin-1-deficient mice showed enhanced ear swelling with enhanced collagen deposition and greater Ly6G⁺ neutrophil recruitment after intra-dermal injection of Pam2CSK4 into pinnae. Using Mas–TRECK mice, which is an MC deletion system based on <span style="font-style:italic;">il4</span> enhancer elements, we also demonstrated that Allergin-1 on MCs is responsible for the Pam2CSK4-induced ear swelling. These results suggest that Allergin-1 on skin MCs suppresses TLR2-induced dermatitis.</span>

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