An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E–mediated immediate hypersensitivity reactions

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.

Inhibitory Immunoreceptors on Mast Cells in Allergy and Inflammation

“…The ear swelling in Allergin-1-defi cient mice was signifi cantly greater than the ear swelling in WT mice during the entire 50 h observation period after the antigen challenge [ 18 ]. Taken together, these results suggest that Allergin-1 negatively regulates IgE-mediated mast cell activation in vivo and suppresses the type 1 immediate hypersensitivity reactions.…”

“…Allergin-1-defi cient mice challenged with TNP-OVA showed signifi cantly lower rectal temperatures than the corresponding WT mice (Fig. 4 ) [ 18 ].…”

“…In agreement with mouse Allergin-1, human Allergin-1L and/or Allergin-1S1 were also expressed in myeloid cell lineages, including monocytes, neutrophils, and dendritic cells, in the peripheral blood. It was noted that, unlike mouse Allergin-1, human Allergin-1L and/or Allergin-1S1 were considerably expressed on peripheral blood basophiles [ 18 ]. Anti-human Allergin-1 monoclonal antibodies (mAbs) EX32 and EX33 recognize an epitope of the fi rst and the second Ig-like domain of Allergin-1L, respectively.…”

“…1 ) [ 18 ]. We also identifi ed two cDNAs encoding Allergin-1 isoforms, which lacked the fi rst or second Ig-like domain in the extracellular portion and were designated Allergin-1 short form 1 (Allergin-1S1) and Allergin-1 short form 2 (Allergin-1S2), respectively (Fig.…”

N-linked Glycosylation Enrichment for In-depth Cell Surface Proteomics of Diffuse Large B-cell Lymphoma Subtypes

“…Allergin-1 is studied in the context of allergic responses where it has been shown to suppress IgE-mediated, mast cell-dependent anaphylaxis in mice. In this same study, it has been shown that allergin-1 was expressed on macrophages, neutrophils and dendritic cells as well as mast cells and/or basophils in both humans and mice (36). Interestingly, allergin-1 was also found to be expressed on human B cells (36).…”