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Janus kinase signaling as risk factor and therapeutic target for severe SARS-CoV-2 infection.
Eur J Immunol. 2021 05; 51(5):1071-1075.EJ

Abstract

Cytokine signaling, especially interferon (IFN) signaling is closely linked to several aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During initial SARS-CoV-2 infection, symptomatic patients present with impaired type I/III IFN-mediated antiviral responses. Interestingly, IFNs regulate the cellular entry receptor for SARS-CoV-2 on epithelial and endothelial cells. As reported recently, critically ill COVID-19 patients show genetic polymorphisms in one IFN receptor gene (IFNRA2) and in a gene locus near the Janus kinase (JAK) TYK2, which is key for IFN, interleukin (IL)-12 and IL-23 signaling, and T helper (Th) 1/Th17 cell-mediated antiviral immune responses. In the advanced stage of the disease, critically ill COVID-19 patients develop a cytokine storm where many inflammatory mediators using the JAK/STAT signaling pathway such as IL-6, IFN-γ, the granulocyte colony-stimulating factor (G-CSF) or IL-2, and chemokines result in an influx of macrophages and neutrophils damaging the lung tissue. The knowledge on the cytokine and JAK/STAT signaling pathways in severe COVID-19 disease explains the promising first results with JAK inhibitors like baricitinib, which not only dampen the inflammation but in the case of baricitinib also affect virus replication and endocytosis in target cells. Here, we summarize the current immunological associations of SARS-CoV-2 infection with cytokine signaling, the JAK/STAT pathway, and the current clinical stage of JAK inhibitors for improving severe COVID-19 disease.

Authors+Show Affiliations

Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany.Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany.Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

33675065

Citation

Solimani, Farzan, et al. "Janus Kinase Signaling as Risk Factor and Therapeutic Target for Severe SARS-CoV-2 Infection." European Journal of Immunology, vol. 51, no. 5, 2021, pp. 1071-1075.
Solimani F, Meier K, Ghoreschi K. Janus kinase signaling as risk factor and therapeutic target for severe SARS-CoV-2 infection. Eur J Immunol. 2021;51(5):1071-1075.
Solimani, F., Meier, K., & Ghoreschi, K. (2021). Janus kinase signaling as risk factor and therapeutic target for severe SARS-CoV-2 infection. European Journal of Immunology, 51(5), 1071-1075. https://doi.org/10.1002/eji.202149173
Solimani F, Meier K, Ghoreschi K. Janus Kinase Signaling as Risk Factor and Therapeutic Target for Severe SARS-CoV-2 Infection. Eur J Immunol. 2021;51(5):1071-1075. PubMed PMID: 33675065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Janus kinase signaling as risk factor and therapeutic target for severe SARS-CoV-2 infection. AU - Solimani,Farzan, AU - Meier,Katharina, AU - Ghoreschi,Kamran, Y1 - 2021/03/22/ PY - 2021/01/08/revised PY - 2021/01/08/received PY - 2021/03/01/accepted PY - 2021/3/7/pubmed PY - 2021/5/20/medline PY - 2021/3/6/entrez KW - JAK inhibitors KW - Janus kinase KW - SARS-CoV-2 KW - cytokine storm KW - severe COVID-19 SP - 1071 EP - 1075 JF - European journal of immunology JO - Eur J Immunol VL - 51 IS - 5 N2 - Cytokine signaling, especially interferon (IFN) signaling is closely linked to several aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During initial SARS-CoV-2 infection, symptomatic patients present with impaired type I/III IFN-mediated antiviral responses. Interestingly, IFNs regulate the cellular entry receptor for SARS-CoV-2 on epithelial and endothelial cells. As reported recently, critically ill COVID-19 patients show genetic polymorphisms in one IFN receptor gene (IFNRA2) and in a gene locus near the Janus kinase (JAK) TYK2, which is key for IFN, interleukin (IL)-12 and IL-23 signaling, and T helper (Th) 1/Th17 cell-mediated antiviral immune responses. In the advanced stage of the disease, critically ill COVID-19 patients develop a cytokine storm where many inflammatory mediators using the JAK/STAT signaling pathway such as IL-6, IFN-γ, the granulocyte colony-stimulating factor (G-CSF) or IL-2, and chemokines result in an influx of macrophages and neutrophils damaging the lung tissue. The knowledge on the cytokine and JAK/STAT signaling pathways in severe COVID-19 disease explains the promising first results with JAK inhibitors like baricitinib, which not only dampen the inflammation but in the case of baricitinib also affect virus replication and endocytosis in target cells. Here, we summarize the current immunological associations of SARS-CoV-2 infection with cytokine signaling, the JAK/STAT pathway, and the current clinical stage of JAK inhibitors for improving severe COVID-19 disease. SN - 1521-4141 UR - https://www.unboundmedicine.com/medline/citation/33675065/Janus_kinase_signaling_as_risk_factor_and_therapeutic_target_for_severe_SARS_CoV_2_infection_ L2 - https://doi.org/10.1002/eji.202149173 DB - PRIME DP - Unbound Medicine ER -