CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses

Abstract

Allergic rhinitis (AR) is an immunoglobulin E-mediated type 2 inflammation of the nasal mucosa that is mainly driven by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). CD226 is a costimulatory molecule associated with inflammatory response and is mainly expressed on T cells, natural killer cells, and monocytes. This study is aimed at elucidating the role of CD226 in allergic inflammatory responses in murine AR using global and CD4+ T cell-specific Cd226 knockout (KO) mice. AR nasal symptoms were assessed based on the frequency of nose rubbing and sneezing. Hematoxylin and eosin and periodic acid–Schiff staining and quantitative real-time PCR methods were used to determine eosinophils, goblet cells, and ILC2-associated mRNA levels in the nasal tissues of mice. CD226 levels on ILC2s were detected using flow cytometry, and an immunofluorescence double staining assay was employed to determine the number of ILC2s in the nasal mucosa. The results showed that global Cd226 KO mice, but not CD4+ T cell-specific Cd226 KO mice, exhibited attenuated AR nasal symptoms. Eosinophil recruitment, goblet cell proliferation, and Th2-inflammatory cytokines were significantly reduced, which resulted in the alleviation of allergic and inflammatory responses. ILC2s in the murine nasal mucosa expressed higher levels of CD226 after ovalbumin stimulation, and CD226 deficiency led to a reduction in the proportion of nasal ILC2s and ILC2-related inflammatory gene expression. Hence, the effect of CD226 on the AR mouse model may involve the regulation of ILC2 function rather than CD4+ T cells.

Blocking group 2 innate lymphoid cell activation and macrophage M2 polarization: potential therapeutic mechanisms in ovalbumin-induced allergic asthma by calycosin

“…IF was used to determine the co-localization of ST2 and CD45 to show the levels of double-positive ILC2s (ST2 + CD45 + ) in the lung tissues [ 48 ]. Besides, the co-localization of EGF-like module-containing mucin-like hormone receptor-like 1 (F4/80) and MRC1 in the lung tissues was detected to show the levels of double-positive M2 macrophages (F4/80 + MRC1+) using IF [ 49 ].…”

Role of autophagy and mitophagy of group 2 innate lymphoid cells in allergic and local allergic rhinitis

“… 9 ILC2s in blood or nasal mucosa are associated with the severity of type 2 inflammation in AR. 10 , 11 , 12 ILC2s play a role in the initial stage of allergic inflammation and interact with T and B cells. Therefore, ILC2s might be involved in the pathogenesis of LAR.…”