Allergin-1 inhibits TLR2-mediated mast cell activation and suppresses dermatitis.
Tsurusaki, S; Tahara-Hanaoka, S; Shibagaki, S; Miyake, S; Imai, M; Shibayama, S; Kubo, M; Shibuya, A
Int Immunol
28
605-609
2015
Show Abstract
TLR2 recognizes cell wall components of Staphylococcus aureus, 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 in vitro 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 il4 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. | 27932517
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An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions.
Hitomi, K; Tahara-Hanaoka, S; Someya, S; Fujiki, A; Tada, H; Sugiyama, T; Shibayama, S; Shibuya, K; Shibuya, A
Nat Immunol
11
601-7
2009
Show Abstract
Anaphylaxis is a life-threatening immediate hypersensitivity reaction triggered by antigen capture by immunoglobulin E (IgE) bound to the high-affinity IgE receptor (FcvarepsilonRI) on mast cells. However, the regulatory mechanism of mast cell activation is not completely understood. Here we identify an immunoglobulin-like receptor, Allergin-1, that contains an immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain, and show it was preferentially expressed on mast cells. Mouse Allergin-1 recruited the tyrosine phosphatases SHP-1 and SHP-2 and the inositol phosphatase SHIP. Coligation of Allergin-1 and FcvarepsilonRI suppressed IgE-mediated degranulation of bone marrow-derived cultured mast cells. Moreover, mice deficient in Allergin-1 developed enhanced passive systemic and cutaneous anaphylaxis. Thus, Allergin-1 suppresses IgE-mediated, mast cell-dependent anaphylaxis in mice. | 20526344
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