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The intrinsic anti-allergic mechanism

The receptor LMIR3-ceramide binding inhibits mast cell activation

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Institute of Medical Science
2012/12/03

Upon engagement of high-affinity immunoglobulin E (IgE) receptor, extracellular ceramide-LMIR3 binding inhibits mast cell activation through tyrosine-phosphorylation of LMIR3. © Jiro Kitaura

Mast cells (MCs) are key effector cells in immunoglobulin E (IgE)-associated immune responses, including anaphylaxis and allergic diseases. However, the inhibitory mechanism that prevents excessive activation of MCs remains elusive. In the present study, a research group led by Assistant Professor Jiro Kitaura and Professor Toshio Kitamura at the Institute of Medical Science, The University of Tokyo, together with Professor Ko Okumura at the Juntendo University School of Medicine and Dr. Hiroshi Kiyonari at the RIKEN Center for Developmental Biology, demonstrated that leukocyte mono-immunoglobulin-like receptor 3 (LMIR3; also called CD300f) is a negative regulator of MC activation in vivo. They found that LMIR3 deficiency exacerbated MC-dependent allergic responses, including anaphylaxis, airway inflammation, and dermatitis, in mice. By using physical binding and functional reporter assays, they identified extracellular ceramide as a physiological ligand for LMIR3 expressed in MC. Their results illustrated an important role for the extracellular ceramide as anti-allergic component that bound to LMIR3, thereby inhibiting MC-dependent allergic responses in vivo. The work substantially advances our understanding of the intrinsic mechanism by which excessive mast cell activation and allergic responses are prevented, and paves the way for the development of new strategies toward prevention, treatment, and management of allergic diseases.

Press release [pdf] (Japanese)

Paper

Kumi Izawa, Yoshinori Yamanishi, Akie Maehara, Mariko Takahashi, Masamichi Isobe, Shinichi Ito, Ayako Kaitani, Toshihiro Matsukawa, Takayuki Matsuoka, Fumio Nakahara, Toshihiko Oki, Hiroshi Kiyonari, Takaya Abe, Ko Okumura, Toshio Kitamura, and Jiro kitaura,
“The Receptor LMIR3 Negatively Regulates Mast Cell Activation and Allergic Responses by Binding to Extracellular Ceramide”,
Immunity (November 16, 2012) Online Edition: 2012/November/2 (Japan time), doi: 10.1016/j.immuni.2012.08.018.
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The Institute of Medical Science

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