Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients.
Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients.
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自噬标志物表达减少和髓源性抑制细胞扩增与重症COVID-19患者T细胞反应不良相关。
DOI：
10.3389/fimmu.2021.614599
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发表时间：
2021
影响因子：
7.3
通讯作者：
Čolić M
中科院分区：
文献类型：
--
作者：
Tomić S;Đokić J;Stevanović D;Ilić N;Gruden-Movsesijan A;Dinić M;Radojević D;Bekić M;Mitrović N;Tomašević R;Mikić D;Stojanović D;Čolić M
Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.
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影响因子：
4.7
作者：
Ahmad, Shamim I.
通讯作者：
Ahmad, Shamim I.
影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
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作者：
Chen MF;Kuan FC;Yen TC;Lu MS;Lin PY;Chung YH;Chen WC;Lee KD
通讯作者：
Lee KD
影响因子：
100.3
作者：
Chen, Zeyu;John Wherry, E.
通讯作者：
John Wherry, E.
影响因子：
3.7
作者：
Cossarizza, Andrea;Gibellini, Lara;Mussini, Cristina
通讯作者：
Mussini, Cristina