Sandig Hilary, McDonald Joanne, Gilmour Jane, Arno Matthew, Lee Tak H, Cousins David J
Medical Research Council--Asthma U.K. Centre in Allergic Mechanisms of Asthma and Genomics Centre, King's College London, London SE1 9RT, United Kingdom.
Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12440-4. doi: 10.1073/pnas.0705457104. Epub 2007 Jul 18.
Th1 and Th2 cells represent the two main functional subsets of CD4(+) T helper cell, and are defined by their cytokine expression. Human Th1 cells express IFNgamma, whilst Th2 cells express IL-4, IL-5, and IL-13. Th1 and Th2 cells have distinct immunological functions, and can drive different immunopathologies. Here, we show that in vitro-differentiated human Th2 cells highly selectively express the gene for pro-melanin-concentrating hormone (PMCH), using real-time RT-PCR, enzyme immunoassay, and Western blot analysis. PMCH encodes the prohormone, promelanin-concentrating hormone (PMCH), which is proteolytically processed to produce several peptides, including the orexigenic hormone melanin-concentrating hormone (MCH). PMCH expression by Th2 cells was activation responsive and increased throughout the 28-day differentiation in parallel with the expression of the Th2 cytokine genes. MCH immunoreactivity was detected in the differentiated Th2 but not Th1 cell culture supernatants after activation, and contained the entire PMCH protein, in addition to several smaller peptides. Human Th1 and Th2 cells were isolated by their expression of IFNgamma and CRTH2, respectively, and the ex vivo Th2 cells expressed PMCH upon activation, in contrast to the Th1 cells. Because Th2 cells are central to the pathogenesis of allergic diseases including asthma, expression of PMCH by activated Th2 cells in vivo may directly link allergic inflammation to energy homeostasis and may contribute to the association between asthma and obesity.
Th1细胞和Th2细胞是CD4(+)辅助性T细胞的两个主要功能亚群，根据其细胞因子表达情况来定义。人类Th1细胞表达干扰素γ（IFNγ），而Th2细胞表达白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和白细胞介素-13（IL-13）。Th1细胞和Th2细胞具有不同的免疫功能，可引发不同的免疫病理反应。在此，我们通过实时逆转录聚合酶链反应（RT-PCR）、酶免疫测定和蛋白质印迹分析表明，体外分化的人类Th2细胞高度选择性地表达促黑素浓缩激素（PMCH）基因。PMCH编码前激素原黑素浓缩激素（PMCH），该前激素经蛋白水解加工产生几种肽，包括促食欲激素黑素浓缩激素（MCH）。Th2细胞中PMCH的表达对激活有反应，并且在整个28天的分化过程中与Th2细胞因子基因的表达平行增加。激活后，在分化的Th2细胞培养上清液中检测到MCH免疫反应性，其中除了几种较小的肽外，还包含完整的PMCH蛋白。人类Th1细胞和Th2细胞分别通过其IFNγ和CRTH2的表达进行分离，与Th1细胞相反，体外Th2细胞激活后表达PMCH。由于Th2细胞在包括哮喘在内的过敏性疾病发病机制中起核心作用，体内激活的Th2细胞中PMCH的表达可能直接将过敏性炎症与能量稳态联系起来，并可能有助于解释哮喘与肥胖之间的关联。
