Decreased CRTH2 Expression and Response to Allergen Re-stimulation on Innate Lymphoid Cells in Patients With Allergen-Specific Immunotherapy

Abstract

PurposeGroup 2 innate lymphoid cells (ILC2s) have been implicated in the pathogenesis of allergic disease. However, the effect of allergen-specific immunotherapy (AIT) on ILCs remains to be clarified. The aim of this study was to evaluate the levels of ILC subsets in allergic rhinitis (AR) patients in response to house dust mite (HDM)-specific immunotherapy.MethodsWe enrolled 37 AR patients undergoing AIT (16 responders and 11 non-responders) for 2 years, 35 HDM AR patients and 28 healthy subjects. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to identify ILC subsets. Stimulation of ILC2s with recombinant allergen-specific protein was used to determine ILC2's activation (CD69 expression).ResultsResponder AIT patients and healthy subjects had a decreased frequency of circulating ILC2s compared to non-responder AIT and AR patients. Conversely, ILC1s from responder AIT patients and healthy subjects showed increased frequency compared to non-responder AIT and AR patients. The frequency of ILC3s natural cytotoxicity receptor (NCR)+ and NCR− in responder AIT patients was significantly lower compared to AR patients and healthy subjects. The ILC1: ILC2 proportion in responder AIT patients was similar to that of healthy subjects. PBMCs from patients who were responders to AIT had a significantly lower expression of the activation marker CD69 on ILC2s in response to allergen re-stimulation compared to AR patients, but no difference compared to non-responder AIT patients and healthy subjects.ConclusionsWe propose that AIT might affect ILC responses. The activation of ILC2s was reduced in AR patients treated with AIT. Our results indicate that a relative ILC1/ILC2 skewed response is a possible key to successful AIT.

Impact of high‐altitude therapy on type‐2 immune responses in asthma patients

“…Prostaglandin D2 activates Th2 cells and ILC2s and is associated with increased expression of CD69. [51][52][53] We demonstrated that, at baseline, PGD2-activated T cell subsets and ILC2s were not different between asthma patients and healthy controls except for CRTH2 + CD8 + T cells. PGD2 and LTE4 regulate diverse genes in CRTH2 + CD8 + T cells inducing type 2 cytokines and many other pro-inflammatory cytokines and chemokines, which could contribute to eosinophilia.…”

Innate Lymphoid Cells in Mucosal Immunity

“…Disrupting this loop with anti-IL-5 antibodies was beneficial for treating chronic rhino-sinusitis in humans (94, 95). More ILC2s have been noted in the peripheral blood of allergic rhinitis patients than in blood from healthy controls (96, 97). Moreover, the response to house dust mite-specific immunotherapy negatively correlated with ILC2 numbers; patients with a good response to the allergen-specific immunotherapy had relatively few ILC2s (97).…”

Diverse Mechanisms of Allergen Specific Immunotherapy

“…On the contrary, ILC1s frequency increased in both groups. As for ILC3 cells, natural cytotoxicity receptor (NCR)+ expression was lower in clinical responders com-pared to healthy control [66]. These results suggest AIT may shift from ILC2s to ILC1s and affects the frequency of ILC3s.…”