Inhibitory receptor gp49B regulates eosinophil infiltration during allergic inflammation

Abstract

gp49B, an Ig-like receptor, negatively regulates the activity of mast cells and neutrophils through cytoplasmic immunoreceptor tyrosine-based inhibition motifs. To characterize the role of gp49B further in vivo, gp49B-deficient mice were tested in two allergic models. Responses to ragweed (RW) challenge in the lung and conjunctiva were assessed in models of allergic inflammation and during an infection with parasitic larvae of the nematode Ascaris suum. Infiltration by inflammatory cells into the lung during allergic responses was under negative control of the inhibitory receptor gp49B. Furthermore, an increase in conjunctival inflammation with a predominance of eosinophils, neutrophils, and degranulated mast cells was observed in RW-sensitized, gp49B-deficient mice, which had been challenged in the eye, as compared with C57BL/6 wild-type (WT) controls. Finally, an increase in allergic inflammation in the lungs of A. suum-infected, RW-sensitized mice was observed upon RW challenge, as compared with C57BL/6 WT controls. The observed influx of eosinophils into mucus membranes is characteristic of allergic asthma and allergic conjunctivitis and may contribute to airway hyper-responsiveness, airway remodeling, and mucus production. Expression of gp49B was detected on peripheral eosinophils of control mice and on eosinophils from lungs of mice treated with RW, suggesting a role for gp49B on eosinophils in dampening allergic inflammatory responses.

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

“…RW sensitization and subsequent antigen challenge is known to affect Th2-specific Ig concentrations in blood (19). Indeed, we found that both IgG1 and IgE serum levels were significantly increased following RW application, whereas IgG2a did not change.…”

“…To elicit a bronchial allergic response, RW sensitization and challenge were used (18,19). C57BL/6J mice were sensitized on d 0 and 5 with 200 μL i.p.…”

“…In animals with established allergies, Th2 responses are already dominant, and we wondered how BMSCs would react to such an environment. In this study we thus examined the effect of BMSCs on Th2-driven allergic reactions in a mouse model of asthma (18,19).…”

The TNF-Family Receptor DR3 is Essential for Diverse T Cell-Mediated Inflammatory Diseases

“…This contrasts with OX40L and FasL, which are hyperexpressed by T cells in the absence of their cognate receptors (C) Cells were extracted from the lungs and analyzed by flow cytometry for the percentage of the indicated subsets out of the total live cell population. Siglec F was used to measure eosinophils as previously described (Norris et al, 2007). invariant 'type-I' NKT (iNKT) cells were enumerated with CD1d-PBS57 tetramer, which identifies Va14Ja18 + T cells responsive to alpha-gal-cer sphingolipid.…”

Chronic inflammation in asthma: a contest of persistence vs resolution

“…The immune-inhibiting effects of members of this class of receptors in allergy are well-known (140), but few studies have assessed the effects of these receptors in classical mouse asthma models. One of these ITIM-bearing Ig-like receptors, gp49B(LILRB4), possesses anti-inflammatory effects in a mouse model of ragweed sensitization and challenge during an infection with the nematode Ascaris suum (141). In summary, stimulating these endogenous pathways could be a promising therapeutic approach, especially in the context of immunotherapy, but not enough is known about the safety and efficacy of interfering with these in humans.…”