The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells

被引：0

作者：

Asada, Nariaki ^{[1
]}

Ginsberg, Pauline ^{[1
]}

Paust, Hans-Joachim ^{[1
]}

Song, Ning ^{[1
]}

Riedel, Jan-Hendrik ^{[1
]}

Turner, Jan-Eric ^{[1
,2
]}

Peters, Anett ^{[1
]}

Kaffke, Anna ^{[1
]}

Engesser, Jonas ^{[1
]}

Wang, Huiying ^{[1
]}

Zhao, Yu ^{[1
,3
]}

Khatri, Robin ^{[1
,3
]}

Gild, Philipp ^{[4
]}

Dahlem, Roland ^{[4
]}

Diercks, Bjoern-Philipp ^{[5
]}

Das, Sarada ^{[6
]}

Ignatova, Zoya ^{[6
]}

Huber, Tobias B. ^{[1
,2
,7
]}

Prinz, Immo ^{[2
,8
]}

Gagliani, Nicola ^{[2
,9
,10
]}

Mittruecker, Hans-Willi ^{[2
,11
]}

Krebs, Christian F. ^{[1
,2
,7
]}

Panzer, Ulf ^{[1
,2
,7
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Dept Med 3, Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Hamburg Ctr Translat Immunol, Hamburg, Germany

[3] Ctr Mol Neurobiol Hamburg, Inst Med Syst Biol, Ctr Biomed AI, Hamburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, Calcium Signalling Grp, Hamburg, Germany

[6] Univ Hamburg, Inst Biochem & Mol Biol, Hamburg, Germany

[7] Univ Med Ctr Hamburg Eppendorf, Hamburg Ctr Kidney Hlth HCKH, Hamburg, Germany

[8] Univ Med Ctr Hamburg Eppendorf, Inst Syst Immunol, Hamburg, Germany

[9] Univ Med Ctr Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Hamburg, Germany

[10] Univ Med Ctr Hamburg Eppendorf I, Dept Med 1, Hamburg, Germany

[11] Univ Med Ctr Hamburg Eppendorf, Inst Immunol, Hamburg, Germany

来源：

NATURE IMMUNOLOGY | 2025年 / 26卷 / 04期

基金：

日本学术振兴会;

关键词：

PSORIASIS;

D O I：

10.1038/s41590-025-02105-x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tissue-resident memory T (TRM) cells are a specialized T cell population that reside in tissues and provide a rapid protective response upon activation. Here, we showed that human and mouse CD4+ TRM cells existed in a poised state and stored messenger RNAs encoding proinflammatory cytokines without protein production. At steady state, cytokine mRNA translation in TRM cells was suppressed by the integrated stress response (ISR) pathway. Upon activation, the central ISR regulator, eIF2 alpha, was dephosphorylated and stored cytokine mRNA was translated for immediate cytokine production. Genetic or pharmacological activation of the ISR-eIF2 alpha pathway reduced cytokine production and ameliorated autoimmune kidney disease in mice. Consistent with these results, the ISR pathway in CD4+ TRM cells was downregulated in patients with immune-mediated diseases of the kidney and the intestine compared to healthy controls. Our results indicated that stored cytokine mRNA and translational regulation in CD4+ TRM cells facilitate rapid cytokine production during local immune response.

引用

页码：557 / 566

页数：28

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