SLAMs Negatively Regulate IL-21 Production in Tfh-Like Cells from Allergic Rhinitis Patients

BACKGROUND: Allergic rhinitis (AR) is characterized by type I hypersensitivity that is mediated by IgE-induced humoral responses. Follicular helper T cells (Tfh) comprise the key helper T cell (Th) subset that promotes antibody production. Signaling lymphocytic activation molecules (SLAMs) participate in regulation of the differentiation and function of Tfh cells, but whether this regulation is involved in the pathogenesis of AR is unknown. METHODS: CD4+CXCR5+ Tfh-like cells from peripheral blood were detected by flow cytometry. The IL-21 and IgE levels in serum were measured by an ELISA. Blood CD4+CXCR5+ Tfh-like cells were sorted and cultured with anti-SLAM mAb in vitro. RESULTS: The frequencies of circulating CD4+CXCR5+ Tfh-like cells appeared virtually unchanged in AR patients, but the expression of SLAMs and SLAM-associated protein (SAP) on circulating Tfh-like cells was significantly decreased. Meanwhile, the level of serum IL-21 was increased in AR patients, and a negative correlation was found between the IL-21 level and SLAM or SAP expression on CD4+CXCR5+ T cells. Treatment with anti-SLAM mAb resulted in reduced IL-21 production by Tfh-like cells in vitro. Additionally, SLAM expression on B cells was significantly decreased, although the percentages of B cells were increased in AR patients. CONCLUSION: SLAMs negatively regulate IL-21 production in CD4+CXCR5+ Tfh-like cells, which contributes to the pathogenesis of AR.