Mary Wilson
Well-known member
Cellular and Molecular Gastroenterology and Hepatology (CMGH)
Official Basic Research Journal of the AGA Institute
January 03, 2025
doi: https://doi.org/10.1016/j.jcmgh.2024.101447.
Marianne R. Spalinger, Golshid Sanati, Pritha Chatterjee, Rong Hai, Jiang Li, Alina N. Santos, Tara M. Nordgren, Michel L. Tremblay, Lars Eckmann, Elaine Hanson, Michael Scharl, Xiwei Wu, Brigid S. Boland, Declan F. McCole
Abstract
Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, triggered a global
pandemic with severe medical and socioeconomic consequences. While fatality rates are higher
among the elderly and those with underlying comorbidities, host factors that promote susceptibility
to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with
certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there
is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases. The aim of our study
was to investigate whether the autoimmunity risk gene, PTPN2, which also confers elevated risk
to develop inflammatory bowel disease (IBD), affects susceptibility to SARS-CoV-2 viral uptake.
Methods: Using samples from PTPN2 genotyped IBD patients, PTPN2-deficient mice, and
human intestinal and lung epithelial cell lines, we investigated how PTPN2 affects expression of
the SARS-CoV-2 receptor ACE2, and uptake of virus-like particles expressing the SARS-CoV2
spike protein and live SARS-CoV-2 virus.
Results: We report that the autoimmune PTPN2 loss-of-function risk variant rs1893217 promotes
expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry of SARS-CoV-2
spike protein and live virus. Elevated ACE2 expression and viral entry were mediated by
increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib.
Conclusion: Collectively, our findings uncover a novel risk biomarker for increased expression
of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent
to mitigate this risk
https://www.cmghjournal.org/action/showPdf?pii=S2352-345X(24)00202-9
Official Basic Research Journal of the AGA Institute
January 03, 2025
doi: https://doi.org/10.1016/j.jcmgh.2024.101447.
Marianne R. Spalinger, Golshid Sanati, Pritha Chatterjee, Rong Hai, Jiang Li, Alina N. Santos, Tara M. Nordgren, Michel L. Tremblay, Lars Eckmann, Elaine Hanson, Michael Scharl, Xiwei Wu, Brigid S. Boland, Declan F. McCole
Abstract
Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, triggered a global
pandemic with severe medical and socioeconomic consequences. While fatality rates are higher
among the elderly and those with underlying comorbidities, host factors that promote susceptibility
to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with
certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there
is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases. The aim of our study
was to investigate whether the autoimmunity risk gene, PTPN2, which also confers elevated risk
to develop inflammatory bowel disease (IBD), affects susceptibility to SARS-CoV-2 viral uptake.
Methods: Using samples from PTPN2 genotyped IBD patients, PTPN2-deficient mice, and
human intestinal and lung epithelial cell lines, we investigated how PTPN2 affects expression of
the SARS-CoV-2 receptor ACE2, and uptake of virus-like particles expressing the SARS-CoV2
spike protein and live SARS-CoV-2 virus.
Results: We report that the autoimmune PTPN2 loss-of-function risk variant rs1893217 promotes
expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry of SARS-CoV-2
spike protein and live virus. Elevated ACE2 expression and viral entry were mediated by
increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib.
Conclusion: Collectively, our findings uncover a novel risk biomarker for increased expression
of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent
to mitigate this risk
https://www.cmghjournal.org/action/showPdf?pii=S2352-345X(24)00202-9