SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development.
SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development.
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正常T细胞发育需要胸腺基质细胞的SOCS3表达。
DOI：
10.3389/fimmu.2021.642173
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发表时间：
2021
影响因子：
7.3
通讯作者：
Rottenberg ME
中科院分区：
文献类型：
--
作者：
Gao Y;Liu R;He C;Basile J;Vesterlund M;Wahren-Herlenius M;Espinoza A;Hokka-Zakrisson C;Zadjali F;Yoshimura A;Karlsson M;Carow B;Rottenberg ME
细胞因子信号转导抑制因子3(SOCS3)是免疫反应和炎症反应的主要调节因子，它负向调节细胞因子信号转导。在此，我们研究了SOCS3在SOCS3FL/F1肌动蛋白-受体小鼠(ΔSOCS3)胸腺T细胞形成中的作用，该小鼠患有他莫昔芬可诱导且普遍存在的SOCS3缺陷。ΔSOCS3胸腺细胞丢失90%，皮质髓质组织改变。胸腺细胞分化和增殖在早期双阴性(CD4-CD8-)细胞阶段受损，在双阳性(CD4+CD8+)细胞阶段细胞凋亡率增加，导致外周器官近期胸腺移行者减少。使用骨髓嵌合体、移植胸腺器官和在胸腺细胞中缺乏SOCS3的小鼠，我们发现胸腺基质细胞而不是胸腺细胞中的表达对T细胞的发育至关重要。我们发现胸腺上皮细胞(TECs)中的SOCS3与E3泛素连接酶TRIM21结合，并且TRIM21−/−小鼠的胸腺细胞数增加。ΔSOCS3TEC显示参与正、负选择和淋巴-基质相互作用的基因表达发生了变化。依赖于SOCS3的信号抑制IL-6受体家族常见的gp130亚单位对于T细胞的形成是多余的。总之，SOCS3在胸腺基质细胞中的表达对T细胞的发育和胸腺结构的维持至关重要。
The suppressor of cytokine signaling 3 (SOCS3) is a major regulator of immune responses and inflammation as it negatively regulates cytokine signaling. Here, the role of SOCS3 in thymic T cell formation was studied in Socs3fl/fl Actin-creER mice (Δsocs3) with a tamoxifen inducible and ubiquitous Socs3 deficiency. Δsocs3 thymi showed a 90% loss of cellularity and altered cortico-medullary organization. Thymocyte differentiation and proliferation was impaired at the early double negative (CD4-CD8-) cell stage and apoptosis was increased during the double positive (CD4+CD8+) cell stage, resulting in the reduction of recent thymic emigrants in peripheral organs. Using bone marrow chimeras, transplanting thymic organoids and using mice deficient of SOCS3 in thymocytes we found that expression in thymic stromal cells rather than in thymocytes was critical for T cell development. We found that SOCS3 in thymic epithelial cells (TECs) binds to the E3 ubiquitin ligase TRIM 21 and that Trim21−/− mice showed increased thymic cellularity. Δsocs3 TECs showed alterations in the expression of genes involved in positive and negative selection and lympho-stromal interactions. SOCS3-dependent signal inhibition of the common gp130 subunit of the IL-6 receptor family was redundant for T cell formation. Together, SOCS3 expression in thymic stroma cells is critical for T cell development and for maintenance of thymus architecture.
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影响因子：
29.4
作者：
Huh WJ;Khurana SS;Geahlen JH;Kohli K;Waller RA;Mills JC
通讯作者：
Mills JC
影响因子：
3.6
作者：
Croom, Hayley A.;Izon, David J.;Starr, Robyn
通讯作者：
Starr, Robyn
影响因子：
1.5
作者：
Guo, CY;Yang, WY;Lobe, CG
通讯作者：
Lobe, CG
影响因子：
5.3
作者：
Forni, Paolo E.;Scuoppo, Claudio;Ponzetto, Carola
通讯作者：
Ponzetto, Carola
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I