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A role for cell-autocrine interleukin-2 in regulatory T-cell homeostasis.
Immunology ( IF 4.9 ) Pub Date : 2020-03-18 , DOI: 10.1111/imm.13194 Amanpreet Singh Chawla 1 , Jasneet Kaur Khalsa 1 , Atika Dhar 1 , Suman Gupta 1 , Danish Umar 1 , Gopalakrishnan Aneeshkumar Arimbasseri 1 , Vineeta Bal 1 , Anna George 1 , Satyajit Rath 1
Immunology ( IF 4.9 ) Pub Date : 2020-03-18 , DOI: 10.1111/imm.13194 Amanpreet Singh Chawla 1 , Jasneet Kaur Khalsa 1 , Atika Dhar 1 , Suman Gupta 1 , Danish Umar 1 , Gopalakrishnan Aneeshkumar Arimbasseri 1 , Vineeta Bal 1 , Anna George 1 , Satyajit Rath 1
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Activated T‐cells make both interleukin‐2 (IL2) and its high‐affinity receptor component CD25. Regulatory CD4 T‐cells (Treg cells) do not make IL2, and the IL2‐CD25 circuit is considered a paracrine circuit crucial in their generation and maintenance. Yet, all T‐cells are capable of making IL2 at some stage during differentiation, making a cell‐intrinsic autocrine circuit additionally possible. When we re‐visited experiments with mixed bone marrow chimeras using a wide range of ratios of wild‐type (WT) and IL2−/− genotype progenitors, we found that, as expected, thymic Treg cells were almost equivalent between WT and IL2−/− genotypes at ratios with WT prominence. However, at WT‐limiting ratios, the IL2−/− genotype showed lower thymic Treg frequencies, indicating a role for cell‐intrinsic autocrine IL2 in thymic Treg generation under IL2‐limiting conditions. Further, peripheral IL2−/− naive CD4 T‐cells showed poor conversion to inducible Tregs (pTregs) both in vivo and in vitro , again indicating a significant role for cell‐intrinsic autocrine IL2 in their generation. Peripherally, the IL2−/− genotype was less prominent at all WT:IL2−/− ratios among both thymic Tregs (tTregs) and pTregs, adoptively transferred IL2−/− Tregs showed poorer survival than WT Tregs did, and RNA‐seq analysis of WT and IL2−/− Tregs showed interesting differences in the T‐cell receptor and transforming growth factor‐beta‐bone morphogenetic protein‐JNK pathways between them, suggesting a non‐titrating role for cell‐intrinsic autocrine IL2 in Treg programming. These data indicate that cell‐intrinsic autocrine IL2 plays significant roles in Treg generation and maintenance.
中文翻译：
细胞自分泌白介素2在调节性T细胞稳态中的作用。
激活的T细胞同时产生白介素2（IL2）及其高亲和力受体组分CD25。调节性CD4 T细胞（Treg细胞）不产生IL2，并且IL2-CD25回路被认为是对其产生和维持至关重要的旁分泌回路。然而，所有T细胞都能够在分化过程中的某个阶段产生IL2，从而使细胞固有的自分泌回路成为可能。当我们再次使用多种野生型（WT）和IL2-/-基因型祖细胞比例的混合骨髓嵌合体进行实验时，我们发现，正如预期的那样，胸腺Treg细胞在WT和IL2- /-基因型与野生型突出率成正比。但是，在野生型限制比率下，IL2-/-基因型显示出较低的胸腺Treg频率，表明细胞内分泌自分泌IL2在IL2限制条件下在胸腺Treg产生中的作用。此外，外周IL2-/-幼稚CD4 T细胞均表现出难以转化为诱导型Treg（pTreg）的能力。在体内和体外，再次表明细胞内分泌自分泌IL2在其生成中起着重要作用。在周围，胸腺Tregs（tTregs）和pTregs在所有WT：IL2-/-比率下，IL2-/-基因型不那么突出，过继转移的IL2-/-Tregs的存活率比WT Tregs差，RNA序列分析WT和IL2-/-Treg的表达在T细胞受体和转化生长因子β骨形态发生蛋白JNK途径之间显示出有趣的差异，表明细胞内源性自分泌IL2在Treg编程中没有调节作用。这些数据表明，细胞内自分泌IL2在Treg的产生和维持中起着重要作用。
更新日期：2020-03-18
中文翻译：
细胞自分泌白介素2在调节性T细胞稳态中的作用。
激活的T细胞同时产生白介素2（IL2）及其高亲和力受体组分CD25。调节性CD4 T细胞（Treg细胞）不产生IL2，并且IL2-CD25回路被认为是对其产生和维持至关重要的旁分泌回路。然而，所有T细胞都能够在分化过程中的某个阶段产生IL2，从而使细胞固有的自分泌回路成为可能。当我们再次使用多种野生型（WT）和IL2-/-基因型祖细胞比例的混合骨髓嵌合体进行实验时，我们发现，正如预期的那样，胸腺Treg细胞在WT和IL2- /-基因型与野生型突出率成正比。但是，在野生型限制比率下，IL2-/-基因型显示出较低的胸腺Treg频率，表明细胞内分泌自分泌IL2在IL2限制条件下在胸腺Treg产生中的作用。此外，外周IL2-/-幼稚CD4 T细胞均表现出难以转化为诱导型Treg（pTreg）的能力。在体内和体外，再次表明细胞内分泌自分泌IL2在其生成中起着重要作用。在周围，胸腺Tregs（tTregs）和pTregs在所有WT：IL2-/-比率下，IL2-/-基因型不那么突出，过继转移的IL2-/-Tregs的存活率比WT Tregs差，RNA序列分析WT和IL2-/-Treg的表达在T细胞受体和转化生长因子β骨形态发生蛋白JNK途径之间显示出有趣的差异，表明细胞内源性自分泌IL2在Treg编程中没有调节作用。这些数据表明，细胞内自分泌IL2在Treg的产生和维持中起着重要作用。
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