Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize antigens derived from riboflavin biosynthesis. In addition to anti-microbial functions, human MAIT cells are associated with cancers, autoimmunity, allergies and inflammatory disorders, although their role is poorly understood. Activated MAIT cells are well known for their rapid release of Th1 and Th17 cytokines, but we have discovered that chronic stimulation can also lead to potent interleukin (IL)-13 expression. We used RNA-seq and qRT-PCR to demonstrate high expression of the IL-13 gene in chronically stimulated MAIT cells, and directly identify IL-13 using intracellular flow cytometry and multiplex bead analysis of MAIT cell cultures. This unexpected finding has important implications for IL-13-dependent diseases, such as colorectal cancer (CRC), that occur in mucosal areas where MAIT cells are abundant. We identify MAIT cells near CRC tumors and show that these areas and precancerous polyps express high levels of the IL-13 receptor, which promotes tumor progression and metastasis. Our data suggest that MAIT cells have a more complicated role in CRC than currently realized and that they represent a promising new target for immunotherapies where IL-13 can be a critical factor.

中文翻译：

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慢性刺激的人类 MAIT 细胞出人意料地是有效的 IL-13 生产者。

粘膜相关不变性 T (MAIT) 细胞是非常规 T 细胞，可识别源自核黄素生物合成的抗原。除了抗微生物功能外，人类 MAIT 细胞还与癌症、自身免疫、过敏和炎症性疾病有关，尽管它们的作用知之甚少。众所周知，活化的 MAIT 细胞会快速释放 Th1 和 Th17 细胞因子，但我们发现慢性刺激也可导致有效的白细胞介素 (IL)-13 表达。我们使用 RNA-seq 和 qRT-PCR 来证明 IL-13 基因在长期刺激的 MAIT 细胞中的高表达，并使用细胞内流式细胞术和 MAIT 细胞培养物的多重珠分析直接鉴定 IL-13。这一意外发现对 IL-13 依赖性疾病具有重要意义，例如结直肠癌 (CRC)、发生在 MAIT 细胞丰富的粘膜区域。我们鉴定了 CRC 肿瘤附近的 MAIT 细胞，并表明这些区域和癌前息肉表达高水平的 IL-13 受体，从而促进肿瘤进展和转移。我们的数据表明 MAIT 细胞在 CRC 中的作用比目前认识到的更为复杂，并且它们代表了免疫疗法的一个有前途的新靶点，其中 IL-13 可能是一个关键因素。