Suurmond Jolien, Habets Kim L L, Dorjée Annemarie L, Huizinga Tom W, Toes René E M
Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands
J Immunol. 2016 Dec 1;197(11):4473-4481. doi: 10.4049/jimmunol.1502640. Epub 2016 Oct 31.
Mast cells (MC) are most well known for their role in innate immune responses. However, MC are increasingly recognized as important regulators of adaptive immune responses, especially in setting the outcome of T cell responses. In this study we determined the effect of MC on cytokine production by naive and memory human Th cells. CD4 T cells were cultured with MC supernatant or control medium, after which cytokine production by T cells was determined. Supernatant of activated MC specifically increased the number of IL-17-producing T cells. This enhancement of Th17 cell number was specifically observed for the memory CD4 T cell population and not for the naive CD4 T cell population. The effect of MC was inhibited for ∼80% by blocking Abs to IL-1β and the rIL-1R antagonist anakinra. Importantly, secretion of active IL-1β by MC was independent of caspase activity, indicating that Th17 cell expansion by MC occurred through inflammasome-independent IL-1β. Together, these studies reveal a role for human MC in setting the outcome of T cell responses through release of caspase-independent IL-1β, and provide evidence for a novel contribution of MC in boosting the Th17 axis in mucosal immune responses.
肥大细胞（MC）在固有免疫反应中的作用最为人熟知。然而，MC越来越被认为是适应性免疫反应的重要调节因子，尤其是在决定T细胞反应的结果方面。在本研究中，我们确定了MC对未活化和记忆性人Th细胞细胞因子产生的影响。将CD4 T细胞与MC上清液或对照培养基一起培养，然后测定T细胞的细胞因子产生情况。活化的MC上清液特异性增加了产生IL-17的T细胞数量。这种Th17细胞数量的增加在记忆性CD4 T细胞群体中特异性观察到，而在未活化的CD4 T细胞群体中未观察到。通过阻断抗IL-1β抗体和重组IL-1R拮抗剂阿那白滞素，MC的作用被抑制了约80%。重要的是，MC分泌活性IL-1β独立于半胱天冬酶活性，这表明MC介导的Th17细胞扩增是通过不依赖炎性小体的IL-1β发生的。总之，这些研究揭示了人MC通过释放不依赖半胱天冬酶的IL-1β在决定T细胞反应结果中的作用，并为MC在增强黏膜免疫反应中的Th17轴方面的新贡献提供了证据。
