van Heerden Dorianne, van Binnendijk Robert S, Tromp Samantha A M, Savelkoul Huub F J, van Neerven R J Joost, den Hartog Gerco
Cell Biology and Immunology Group, Wageningen University, 6700 AH Wageningen, The Netherlands.
Center for Immunology of Infectious Diseases and Vaccination, National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands.
Int J Mol Sci. 2021 Mar 30;22(7):3592. doi: 10.3390/ijms22073592.
Thymic stromal lymphopoietin (TSLP) contributes to asthmatic disease. The concentrations of protective IgA may be reduced in the respiratory tract of asthma patients. We investigated how homeostatic short TSLP (shTSLP) and asthma-associated long TSLP (loTSLP) regulate IgA production. B cells from healthy donors were stimulated in the presence or absence of shTSLP or loTSLP; the concentrations of IgA, IgM, IgE, and IgG antibodies were determined in cell culture supernatants; and B cells were analyzed by flow cytometry. LoTSLP, but not shTSLP, suppressed the secretion of IgA but not of IgE. The type 2 cytokine IL-4, which in addition to loTSLP contributes to asthmatic disease, did not affect the production of IgA or the frequency of IgA+ B cells. Instead, IL-4 increased IgG production, especially of the subclasses IgG2 and IgG4. LoTSLP inhibited IgA secretion by sorted memory B cells but not by naïve B cells. Although loTSLP inhibited IgA production, the vitamin A metabolite retinoic acid promoted the secretion of IgA, also in the presence of loTSLP, suggesting that vitamin A may promote IgA production in asthma. Our data demonstrate that asthma-associated loTSLP negatively regulates the secretion of IgA, which may negatively impact the surveillance of mucosal surfaces in asthma.
胸腺基质淋巴细胞生成素（TSLP）与哮喘疾病相关。哮喘患者呼吸道中具有保护作用的IgA浓度可能会降低。我们研究了稳态短链TSLP（shTSLP）和与哮喘相关的长链TSLP（loTSLP）如何调节IgA的产生。在有或无shTSLP或loTSLP的情况下刺激健康供体的B细胞；测定细胞培养上清液中IgA、IgM、IgE和IgG抗体的浓度；并通过流式细胞术分析B细胞。LoTSLP而非shTSLP抑制了IgA的分泌，但不影响IgE的分泌。2型细胞因子IL-4除了与loTSLP一起导致哮喘疾病外，并不影响IgA的产生或IgA+B细胞的频率。相反，IL-4增加了IgG的产生，尤其是IgG2和IgG4亚类。LoTSLP抑制分选的记忆B细胞而非幼稚B细胞分泌IgA。尽管loTSLP抑制IgA的产生，但维生素A代谢产物视黄酸在有loTSLP存在的情况下也促进了IgA的分泌，这表明维生素A可能促进哮喘中IgA的产生。我们的数据表明，与哮喘相关的loTSLP对IgA的分泌具有负调节作用，这可能对哮喘中黏膜表面的监测产生负面影响。
