IL-13Rα2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis.
IL-13Rα2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis.
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DOI：
10.1136/gutjnl-2013-305671
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发表时间：
2014-11
期刊：
影响因子：
24.5
通讯作者：
Strober W
中科院分区：
文献类型：
--
作者：
Fuss IJ;Joshi B;Yang Z;Degheidy H;Fichtner-Feigl S;de Souza H;Rieder F;Scaldaferri F;Schirbel A;Scarpa M;West G;Yi C;Xu L;Leland P;Yao M;Mannon P;Puri RK;Fiocchi C;Strober W
先前的研究表明，溃疡性结肠炎（UC）与固有层非恒定（II型）NKT细胞的存在有关，这些细胞产生白细胞介素 - 13（IL - 13）并介导上皮细胞毒性。在此，我们试图确定刺激NKT细胞的抗原，并对UC固有层中的这些细胞进行定量。
采用负载硫脂的四聚体和基于量子点的流式细胞术及染色法检测UC固有层单核细胞（LPMCs）中的II型NKT细胞。用硫脂糖脂培养UC LPMCs，以确定硫脂对上皮细胞毒性、IL - 13产生以及白细胞介素 - 13受体α2（IL - 13Rα2）表达的诱导作用。采用盲法基于量子点的表型分析来评估UC LPMC中IL - 13Rα2、CD161和IL - 13的表达。
大约36%的UC LPMC对硫脂四聚体呈阳性，而对照LPMC即使有阳性的也极少。经检测，阳性细胞同时也呈CD3和IL - 13Rα2阳性。用硫脂糖脂培养UC LPMC表明，硫脂刺激UC LPMC产生IL - 13，并诱导UC CD161⁺ LPMC对活化上皮细胞的细胞毒性；此外，硫脂诱导IL - 13Rα2表达增强。最后，使用多色量子点染色技术对UC LPMC进行盲法表型分析表明，大约60%的LPMC同时具有IL - 13Rα2和CD161，且这些细胞中的大多数也产生IL - 13。
这些研究表明，UC固有层充满了对硫脂糖脂有反应且具有IL - 13Rα2的II型NKT细胞。由于硫脂是一种自身抗原，这些数据提示自身免疫反应参与了UC的发病机制。
Previous studies have shown that ulcerative colitis (UC) is associated with the presence of lamina propria non-invariant (Type II) NKT cells producing IL-13 and mediating epithelial cell cytotoxicity. Here we sought to define the antigen(s) stimulating the NKT cells and to quantitate these cells in the UC lamina propria. Detection of Type II NKT cells in UC lamina propria mononuclear cells (LPMCs) with lysosulfatide loaded tetramer and quantum dot-based flow cytometry and staining. Culture of UC LPMCs with lyso-sulfatide glycolipid to determine sulfatide induction of epithelial cell cytotoxicity, IL-13 production and IL-13Rα2 expression. Blinded quantum dot-based phenotypic analysis to assess UC LPMC expression of IL-13Rα2, CD161 and IL-13. Approximately 36% of UC LPMC were lyso-sulfatide tetramer positive whereas few if any control LPMC were positive. When tested, the positive cells were also CD3 and IL-13Rα2 positive. Culture of UC LPMC with lyso-sulfatide glycolipid showed that sulfatide stimulates UC LPMC production of IL-13 and induces UC CD161+ LPMC-mediated cytotoxicity of activated epithelial cells; in addition, lyso-sulfatide induces enhanced expression of IL-13Rα2. Finally, blinded phenotypic analysis of UC LP MC using multi-color quantum dot staining technology showed that approximately 60% of the LPMC bear both IL-13Rα2 and CD161 and most of these cells also produce IL-13. These studies show that UC lamina propria is replete with Type II NKT cells responsive to lyso-sulfatide glycolipid and bearing IL-13Rα2. Since lyso-sulfatide is a self-antigen these data suggest that an autoimmune response is involved in UC pathogenesis.