Skin and gut imprinted T helper cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity

We developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of T helper cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system in a model for Multiple Sclerosis are distinct. Comparison of DNA accessibility by Omni-ATAC-seq in sorted effector i- and m-T cells (mD2RED CD4+ CD44high) and naive i- and m-T cells (mD2RED CD4+ CD44int) from spleen.

本研究构建了一套实验框架，旨在验证“系统性免疫区室中的致敏位点是远端器官中辅助T细胞诱导免疫病理的决定性因素”这一假说。通过对腹股沟（i）或肠道引流肠系膜（m）淋巴结内的抗原特异性T细胞进行位点特异性体内标记，我们证实：在多发性硬化（Multiple Sclerosis）模型中，从炎症性中枢神经系统分离得到的i-T细胞与m-T细胞存在显著差异。本研究通过Omni-ATAC-seq技术，对从脾脏中分选获得的效应性i-T细胞、m-T细胞（mD2RED CD4+ CD44high）以及初始性i-T细胞、m-T细胞（mD2RED CD4+ CD44int）的DNA可及性进行了比较分析。