RT Journal Article SR Electronic T1 Distinct lung-homing receptor expression and activation profiles on NK cell and T cell subsets in COVID-19 and influenza JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.01.13.426553 DO 10.1101/2021.01.13.426553 A1 Demi Brownlie A1 Inga Rødahl A1 Renata Varnaite A1 Hilmir Asgeirsson A1 Hedvig Glans A1 Sara Falck-Jones A1 Sindhu Vangeti A1 Marcus Buggert A1 Hans-Gustaf Ljunggren A1 Jakob Michaëlsson A1 Sara Gredmark-Russ A1 Anna Smed-Sörensen A1 Nicole Marquardt YR 2021 UL http://biorxiv.org/content/early/2021/01/13/2021.01.13.426553.abstract AB Respiratory viral infections with SARS-CoV-2 or influenza viruses commonly induce a strong infiltration of immune cells into the lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, little is known about how blood natural killer (NK) cells and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Using 28-colour flow cytometry and re-analysis of published RNA-seq datasets, we provide a detailed comparative analysis of NK cells and T cells in peripheral blood from moderately sick COVID-19 and influenza patients, focusing on the expression of chemokine receptors known to be involved in leukocyte recruitment to the lung. The results reveal a predominant role for CXCR3, CXCR6, and CCR5 in COVID-19 and influenza patients, mirrored by scRNA-seq signatures in peripheral blood and bronchoalveolar lavage from publicly available datasets. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation as compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza as compared to COVID-19. Together, our results indicate migration of functionally competent CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells to the lungs in moderate COVID-19 and influenza patients, identifying potential common targets for future therapeutic interventions in respiratory viral infections.Author summary The composition of in particular CXCR3+ and/or CXCR6+ NK cells and T cells is altered in peripheral blood upon infection with SARS-CoV-2 or influenza virus in patients with moderate disease. Lung-homing receptor-expression is biased towards phenotypically activated NK cells and T cells, suggesting a functional role for these cells co-expressing in particular CXCR3 and/or CXCR6 upon homing towards the lung.Competing Interest StatementThe authors have declared no competing interest.