Aquaporin-1 expression in immune cells is required for generation of adaptive immunity 9343

Abstract Description The mechanisms underlying the diversity in adaptive immunity remain multifactorial and poorly understood. To identify novel contributing mechanisms, we evaluated bulk RNA sequencing data from human subjects receiving an intradermal fractional inactivated polio vaccine (fIPV) with and without addition of double mutant of E. coli enterotoxin (dmLT) adjuvant. We compared these findings to a dmLT-treated monocyte cell line (THP-1). Screening for shared genetic changes in these two experimental settings identified altered expression of aquaporin-1 (AQP1) and major histocompatibility complex-II gene HLA-DR. Pharmacological inhibition of AQP1 prevented dmLT-induced HLA-DR upregulation in THP-1 cells, suggesting AQP1 is necessary for HLA-DR shuttling to the cell surface and antigen presentation. To further understand the role of AQP-1, we generated a conditional knockout using a CD19-cre/AQP1-flox (AQP1-CD19) mouse. These mice were vaccinated with tetanus toxoid (TT) and dmLT adjuvant. Serum analyses showed that AQP1-CD19 mice expressed reduced levels of CD19 B-cells, were unable to develop any TT-specific IgG post-vaccination and had decreased total IgG and IgM compared to WT mice. Thus, AQP1 in B-cells seems to be required for B-cell proliferation and antibody generation. Thus, AQP1 looks to have a major and previously unknown role as a critical immune mediator specific involved in both antigen presentation and antibody development. Funding Sources Funding for this study was provided by NIH/NIAID Award Numbers R56AI143937-01A R01AI166682-01 to EBN Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)