Allergin-1 Immunoreceptor Suppresses House Dust Mite–Induced Allergic Airway Inflammation

Abstract

House dust mite (HDM) allergens are leading causes of allergic asthma characterized by Th2 responses. The lung-resident CD11b + dendritic cells (DCs) play a key role in Th2 cell development in HDM-induced allergic asthma. However, the regulatory mechanism of HDM-induced CD11b + DC activation remains incompletely understood. In this study, we demonstrate that mice deficient in an inhibitory immunoreceptor, Allergin-1, showed exacerbated HDM-induced airway eosinophilia and serum IgE elevation. By using bone marrow-chimeric mice that were sensitized with adoptively transferred HDM-stimulated wild-type or Allergin-1-deficient CD11b + bone marrow-derived cultured DCs (BMDCs), followed by challenge with HDM, we show that Allergin-1 on the BMDCs suppressed HDM-induced allergic airway inflammation. We also show that Allergin-1 suppressed HDM-induced PGE 2 production from CD11b + BMDCs by inhibiting Syk tyrosine kinase activation through recruitment of SHP-1, subsequently leading to negative regulation of Th2 responses. These results suggest that Allergin-1 plays an important role in regulation of HDM-induced allergic airway inflammation.

Differential isoform expression of Allergin‐1 during acute and chronic inflammation

“…While collagen(‐like) molecules are known ligands of LAIR‐1, the ligand of Allergin‐1 is unknown. However, airway hyperresponsiveness and inflammation in response to house dust mites are suppressed by Allergin‐1 on mast cells and lung‐resident CD11b+ dendritic cells, respectively 10,12 . This suggests that ligands for Allergin‐1 are present in lung tissue.…”

“…Allergy inhibitory receptor 1 (Allergin‐1) is an immunoreceptor tyrosine‐based inhibitory motif (ITIM)‐bearing immunoglobulin (Ig)‐like receptor that is primarily expressed on B cells (in humans) and myeloid cells (in humans and mice), including all types of granulocytes 7 . The inhibitory function of Allergin‐1 on mast cells and basophilic granulocytes and its regulatory role in allergic diseases has been demonstrated 8–12 . A potential regulatory function of Allergin‐1 on neutrophilic granulocytes and monocytes has received less scrutiny, however.…”

“… 7 The inhibitory function of Allergin‐1 on mast cells and basophilic granulocytes and its regulatory role in allergic diseases has been demonstrated. 8 , 9 , 10 , 11 , 12 A potential regulatory function of Allergin‐1 on neutrophilic granulocytes and monocytes has received less scrutiny, however. Since neutrophils highly express Allergin‐1 and are regulated by other ITIM‐bearing inhibitory receptors, such as leukocyte‐associated immunoglobulin‐like receptor 1 (LAIR‐1) and signal inhibitory receptor on leukocytes 1 (SIRL‐1), an inhibitory function of Allergin‐1 on neutrophils seems plausible.…”

The Effect of Lipid Metabolism on CD4+ T Cells

“…In an allergy-induced asthma model, researchers found that when PGE2 production is suppressed, the Th2 cell transcription factor GATA3 was negatively regulated, indicating that PGE2 is required in Th2 cell activation [ 62 ]. PGE2 was also found to induce Tfh cell differentiation in prostate cancer [ 63 ].…”

Immunoglobulin E-Dependent Activation of Immune Cells in Rhinovirus-Induced Asthma Exacerbation

“…Numerous studies have been conducted on HDM-induced airway inflammation in murine models. While most studies failed to mention on the role of IgE or mast cells (64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79), a recent study showed that HDM-induced airway inflammation is not dependent on IgE or FcεRI (80). In this Perspective, we will overview fundamental aspects of IgE, IgE receptors, and mechanisms of anti-IgE mAb's function.…”