Roles of CCR10-regulated mucosal IgA responses in lung SARS-CoV-2 infection clearance and pathogenesis 3261

Abstract Description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded positive sense RNA virus that is responsible for the COVID-19 pandemic. While most patients can mount proper immune responses to control the viral infection, a small percentage of the population develop severe disease symptoms which results in dysregulated immune activation that leads to injury of the lung and other organs. Severe COVID-19 patients have an increased recruitment and accumulation of CCR10+ antibody-secreting plasma cells (IgA-ASCs) in the lungs compared to healthy and mild patients, suggesting a role of CCR10-regulated mucosal IgA responses in SARS-CoV-2 infection. CCR10 is a chemokine receptor that can regulate localization and maintenance of IgA-ASCs through interaction with its ligand CCL28, which is highly expressed in mucosal tissues. We investigated how CCR10-regulated mucosal IgA responses are involved in clearance of SARS-CoV-2 viral infection versus immunopathological development using CCR10-knockout (KO) mice. Compared to CCR10-sufficent mice, SARS-CoV-2 infected CCR10-KO mice developed more severe lung pathology associated with impaired localization of IgA+ plasma cells and reduced antigen-specific IgA responses in lungs. On the hand, CCR10-KO mice were still able to control SARS-CoV-2 infections. Our findings revealed a primary role of CCR10-regulated mucosal IgA responses in protection against over-active immune pathological damage to the lung by the viral infection. Funding Sources Supported by NIH R21 AI169430; R01 AI174181-01A1S1 Topic Categories Mucosal and Regional Immunology (MUC)