STAT1 Represses Cytokine-Producing Group 2 and Group 3 Innate Lymphoid Cells during Viral Infection.
STAT1 Represses Cytokine-Producing Group 2 and Group 3 Innate Lymphoid Cells during Viral Infection.
复制标题
DOI：
10.4049/jimmunol.1601984
复制
发表时间：
2017-07-15
期刊：
影响因子：
--
通讯作者：
Peebles RS Jr
中科院分区：
文献类型：
--
作者：
Stier MT;Goleniewska K;Cephus JY;Newcomb DC;Sherrill TP;Boyd KL;Bloodworth MH;Moore ML;Chen K;Kolls JK;Peebles RS Jr
在病毒感染期间，适当协调不同的免疫反应臂是促进有效的病毒清除同时限制免疫病理的关键。然而，指导这种协调的信号和机制尚不完全清楚。干扰素在病毒感染期间大量产生，并通过信号换能器和转录激活子1 （STAT1）具有收敛信号。我们假设病毒感染期间的STAT1信号通路会调节先天淋巴样细胞（ILC）的平衡，先天淋巴样细胞是一种不同类型的淋巴细胞，可以对包括病毒感染在内的环境损害做出反应，具有抗病毒或免疫病理功能的潜力。在呼吸道合胞病毒（RSV）感染期间，与RSV感染的WT小鼠相比，stat1缺陷小鼠的抗病毒IFNγ+ ILC1数量减少，免疫病理IL-5+和IL-13+ ILC2和IL-17A+ ILC3数量增加。利用骨髓嵌合小鼠，我们发现在stat1缺陷小鼠的病毒感染过程中，ILC内源性和ILC外源性因素都是导致ILC失调的原因。关于ilc外源性机制，我们发现与WT小鼠相比，在RSV感染期间，stat1缺陷小鼠IL-33和IL-23的表达显著增加，这两种细胞因子分别促进ILC2和ILC3。此外，在rsv感染期间，破坏IL-33或IL-23信号通路会减弱stat1缺陷小鼠产生的细胞因子ILC2和ILC3反应。总的来说，这些数据表明STAT1是病毒感染期间通过IL-33和IL-23的il - c外源性调节产生细胞因子ILC反应的关键协调者。
The appropriate orchestration of different arms of the immune response is critical during viral infection to promote efficient viral clearance while limiting immunopathology. However, the signals and mechanisms that guide this coordination are not fully understood. Interferons are produced at high levels during viral infection and have convergent signaling through signal transducer and activator of transcription 1 (STAT1). We hypothesized that STAT1 signaling during viral infection would regulate the balance of innate lymphoid cells (ILC), a diverse class of lymphocytes that are poised to respond to environmental insults including viral infections with the potential for both anti-viral or immunopathologic functions. During infection with respiratory syncytial virus (RSV), STAT1-deficient mice had reduced numbers of anti-viral IFNγ+ ILC1 and increased numbers of immunopathologic IL-5+ and IL-13+ ILC2 and IL-17A+ ILC3 compared to RSV-infected WT mice. Using bone marrow chimeric mice, we found that both ILC-intrinsic and ILC-extrinsic factors were responsible for this ILC dysregulation during viral infection in STAT1-deficient mice. Regarding ILC-extrinsic mechanisms, we found that STAT1-deficient mice had significantly increased expression of IL-33 and IL-23, cytokines that promote ILC2 and ILC3 respectively, compared to WT mice during RSV infection. Moreover, disruption of IL-33 or IL-23 signaling attenuated cytokine-producing ILC2 and ILC3 responses in STAT1-deficient mice during RSV-infection. Collectively, these data demonstrate that STAT1 is a key orchestrator of cytokine-producing ILC responses during viral infection via ILC-extrinsic regulation of IL-33 and IL-23.
登录
查看更多内容
在流感病毒感染过程中，第2组IL-5的先天淋巴样细胞的产生受NKT细胞的调节。
影响因子：
6.7
作者：
Gorski SA;Hahn YS;Braciale TJ
通讯作者：
Braciale TJ
影响因子：
32.4
作者：
Halim, Timotheus Y. F.;Krauss, Ramona H.;Takei, Fumio
通讯作者：
Takei, Fumio
影响因子：
7
作者：
Boisson-Dupuis S;Kong XF;Okada S;Cypowyj S;Puel A;Abel L;Casanova JL
通讯作者：
Casanova JL
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
9.1
作者：
Depner M;Fuchs S;Raabe J;Frede N;Glocker C;Doffinger R;Gkrania-Klotsas E;Kumararatne D;Atkinson TP;Schroeder HW Jr;Niehues T;Dückers G;Stray-Pedersen A;Baumann U;Schmidt R;Franco JL;Orrego J;Ben-Shoshan M;McCusker C;Jacob CM;Carneiro-Sampaio M;Devlin LA;Edgar JD;Henderson P;Russell RK;Skytte AB;Seneviratne SL;Wanders J;Stauss H;Meyts I;Moens L;Jesenak M;Kobbe R;Borte S;Borte M;Wright DA;Hagin D;Torgerson TR;Grimbacher B
通讯作者：
Grimbacher B