Identification of a T follicular helper cell subset that drives anaphylactic IgE
Identification of a T follicular helper cell subset that drives anaphylactic IgE
复制标题
DOI：
10.1126/science.aaw6433
复制
发表时间：
2019-08-30
期刊：
影响因子：
56.9
通讯作者：
Eisenbarth, Stephanie C.
中科院分区：
文献类型：
--
作者：
Gowthaman, Uthaman;Chen, Jennifer S.;Eisenbarth, Stephanie C.
高亲和力免疫球蛋白E（IgE）的交联导致危及生命的过敏反应。然而，诱导B细胞产生IgE以响应过敏原的细胞机制仍然知之甚少。滤泡辅助性T（T-FH）细胞指导由B细胞产生的抗体的亲和力和同种型。尽管T-FH细胞衍生的白细胞介素-4（IL-4）对于IgE的产生是必需的，但这是不够的。我们报告了一种罕见的产生IL-13的T-FH细胞存在于小鼠和人的IgE过敏原，但不是当过敏原特异性IgE不存在或只有低亲和力。这些“T（FH）13”细胞具有不寻常的细胞因子谱（IL-13（hi）IL-4（hi）IL-5（hi）IL-21（lo））并共表达转录因子BCL 6和GATA 3。T（FH）13细胞是产生高亲和力而非低亲和力IgE和随后的过敏原诱导的过敏反应所必需的。阻断T（FH）13细胞可能是改善过敏反应的另一种治疗靶点。
Cross-linking of high-affinity immunoglobulin E (IgE) results in the life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE in response to allergens remain poorly understood. T follicular helper (T-FH) cells direct the affinity and isotype of antibodies produced by B cells. Although T-FH cell-derived interleukin-4 (IL-4) is necessary for IgE production, it is not sufficient. We report a rare population of IL-13-producing T-FH cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These "T(FH)13" cells have an unusual cytokine profile (IL-13(hi)IL-4(hi)IL-5(hi)IL-21(lo)) and coexpress the transcription factors BCL6 and GATA3. T(FH)13 cells are required for production of high-but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking T(FH)13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.