T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice.
T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice.
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T 细胞信号传导和 Treg 功能障碍与 IL-2Rα-KO 自身免疫小鼠的疾病动力学相关。
DOI：
10.1038/s41598-020-78975-y
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发表时间：
2020-12-15
影响因子：
4.6
通讯作者：
Hoyer KK
中科院分区：
文献类型：
--
作者：
Mullins GN;Valentine KM;Al-Kuhlani M;Davini D;Jensen KDC;Hoyer KK
IL-2 R α部分包含IL-2的高亲和力受体，IL-2是一种在免疫增殖、活化和调节中重要的细胞因子。IL-2 R α缺陷小鼠（IL-2 R α-KO）在18 - 80日龄之间发生全身性自身免疫性疾病并死于严重贫血。这些小鼠发展出动力学上不同的自身免疫性进展，大约四分之一在21天龄时死亡，一半在30天后死亡。本研究旨在确定免疫参数和细胞因子信号传导，以区分发展早期与晚期自身免疫性疾病的IL-2 R α-KO小鼠队列。为了研究这些差异，我们评估了自身免疫性溶血性贫血（AIHA）和骨髓衰竭期间的全血细胞计数（CBC）、红细胞抗体结合、T细胞数量和活化、造血祖细胞变化和信号动力学。我们确定了几个变化，当结合起来，与疾病动力学。早发性疾病与抗RBC抗体、血细胞比容降低和IL-7信号传导减少相关。CD 8调节性T细胞（TCD 8）在早期疾病中具有增强的凋亡。此外，早期和晚期终末期疾病虽然很大程度上相似，但有几个差异，表明驱动自身免疫性疾病动力学的不同机制。因此，由T细胞信号传导驱动的IL-2 R α-KO疾病病理率促进效应T细胞活化和扩增以及Treg功能障碍。
IL-2Rα, in part, comprises the high affinity receptor for IL-2, a cytokine important in immune proliferation, activation, and regulation. IL-2Rα deficient mice (IL-2Rα-KO) develop systemic autoimmune disease and die from severe anemia between 18 and 80 days of age. These mice develop kinetically distinct autoimmune progression, with approximately a quarter dying by 21 days of age and half dying after 30 days. This research aims to define immune parameters and cytokine signaling that distinguish cohorts of IL-2Rα-KO mice that develop early- versus late-stage autoimmune disease. To investigate these differences, we evaluated complete blood counts (CBC), antibody binding of RBCs, T cell numbers and activation, hematopoietic progenitor changes, and signaling kinetics, during autoimmune hemolytic anemia (AIHA) and bone marrow failure. We identified several alterations that, when combined, correlate to disease kinetics. Early onset disease correlates with anti-RBC antibodies, lower hematocrit, and reduced IL-7 signaling. CD8 regulatory T cells (Tregs) have enhanced apoptosis in early disease. Further, early and late end stage disease, while largely similar, had several differences suggesting distinct mechanisms drive autoimmune disease kinetics. Therefore, IL-2Rα-KO disease pathology rates, driven by T cell signaling, promote effector T cell activation and expansion and Treg dysfunction.
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影响因子：
12.8
作者：
Gravano DM;Al-Kuhlani M;Davini D;Sanders PD;Manilay JO;Hoyer KK
通讯作者：
Hoyer KK
DOI：
10.4049/jimmunol.1003961
发表时间：
2011-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castro I;Yu A;Dee MJ;Malek TR
通讯作者：
Malek TR
DOI：
10.1084/jem.20062381
发表时间：
2007-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dooms H;Wolslegel K;Lin P;Abbas AK
通讯作者：
Abbas AK
影响因子：
4.4
作者：
Evans, Jamie G.;Chavez-Rueda, Karina A.;Mauri, Claudia
通讯作者：
Mauri, Claudia
影响因子：
4.4
作者：
Katzman, Shoshana D.;Gallo, Eugenio;Abbas, Abul K.
通讯作者：
Abbas, Abul K.