PD-1 and ICOS counter-regulate tissue resident regulatory T cell development and IL-10 production during flu.
PD-1 and ICOS counter-regulate tissue resident regulatory T cell development and IL-10 production during flu.
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DOI：
10.3389/fimmu.2022.984476
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发表时间：
2022
影响因子：
7.3
通讯作者：
Huang, Weishan
中科院分区：
文献类型：
--
作者：
McGee, Michael C.;Zhang, Tianyi;Magazine, Nicholas;Islam, Rezwanul;Carossino, Mariano;Huang, Weishan
表达转录因子Foxp3（Treg细胞）的调节性T细胞是一种高度异源性的免疫调节细胞，对于维持免疫稳态和预防感染过程中的免疫病理至关重要。组织常驻Treg（TR-Treg）细胞保持在非淋巴组织中，并已被证明可以抑制促炎性组织驻留T细胞反应并促进组织修复。人群重复暴露于流感感染中，肺组织常驻效应T细胞反应与流感诱导的长期肺后遗症有关。在重复和/或长期流感感染过程中Treg细胞发育和分子特征的动力学尚不清楚。利用FOXP3RFP/IL-10GFP双报告小鼠模型以及血管内荧光在体内标记中，我们表征了TR-Treg细胞对重复性杂型型流感感染的反应。我们发现肺组织常驻Treg细胞积累，并在原发性和继发感染后表达高水平的共抑制性和共刺激受体。 PD-1或ICOS信号传导的阻断表明，在继发流感感染期间，PD-1和ICOS信号通路会反调节TR-Treg细胞扩展和IL-10产生。此外，与常规的CD4+组织驻留记忆T细胞相比，病毒特异性的Treg细胞反应在继发感染期间显示出不同的动力学。我们的结果提供了对重复流感感染期间组织常驻FOXP3+调节性T细胞反应的见解，这可能适用于其他呼吸道传染病，例如结核病和共证。
Regulatory T cells that express the transcription factor Foxp3 (Treg cells) are a highly heterogenous population of immunoregulatory cells critical for maintaining immune homeostasis and preventing immunopathology during infections. Tissue resident Treg (TR-Treg) cells are maintained within nonlymphoid tissues and have been shown to suppress proinflammatory tissue resident T cell responses and promote tissue repair. Human populations are repetitively exposed to influenza infections and lung tissue resident effector T cell responses are associated with flu-induced long-term pulmonary sequelae. The kinetics of TR-Treg cell development and molecular features of TR-Treg cells during repeated and/or long-term flu infections are unclear. Utilizing a Foxp3RFP/IL-10GFP dual reporter mouse model along with intravascular fluorescent in vivo labeling, we characterized the TR-Treg cell responses to repetitive heterosubtypic influenza infections. We found lung tissue resident Treg cells accumulated and expressed high levels of co-inhibitory and co-stimulatory receptors post primary and secondary infections. Blockade of PD-1 or ICOS signaling reveals that PD-1 and ICOS signaling pathways counter-regulate TR-Treg cell expansion and IL-10 production, during secondary influenza infection. Furthermore, the virus-specific TR-Treg cell response displayed distinct kinetics, when compared to conventional CD4+ tissue resident memory T cells, during secondary flu infection. Our results provide insight into the tissue resident Foxp3+ regulatory T cell response during repetitive flu infections, which may be applicable to other respiratory infectious diseases such as tuberculosis and COVID.
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抗原特异性记忆调节CD4+ FOXP3+ T细胞控制对流感病毒感染的记忆反应。
DOI：
10.4049/jimmunol.1203140
发表时间：
2013-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brincks EL;Roberts AD;Cookenham T;Sell S;Kohlmeier JE;Blackman MA;Woodland DL
通讯作者：
Woodland DL
影响因子：
4.4
作者：
Hogan, RJ;Usherwood, EJ;Woodland, DL
通讯作者：
Woodland, DL
影响因子：
32.4
作者：
Delacher, Michael;Imbusch, Charles D.;Feuerer, Markus
通讯作者：
Feuerer, Markus
影响因子：
8
作者：
Barros L;Ferreira C;Veldhoen M
通讯作者：
Veldhoen M
DOI：
10.1073/pnas.0911573106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Gigoux, Mathieu;Shang, Jijun;Suh, Woong-Kyung
通讯作者：
Suh, Woong-Kyung