Tertiary lymphoid follicles in the human nasal mucosa are inductive sites for humoral immunity 9253

Abstract Description The nasal mucosa is the first contact site for inhaled pathogens and is a critical physical barrier for protection against pathogen entry. Importantly, immune cells at this site contribute to the localized defense against infection in the upper respiratory tract. We currently have limited knowledge of the spatial distribution of immune cells within this tissue and whether it acts as an inductive site to support local adaptive immune responses. To address this, we performed spatial transcriptomics on human nasal samples using the Xenium in situ platform. We discovered several tertiary lymphoid follicles (TLFs) in the mucosa on the ethmoid bone. The TLF was loosely organized into B and T cell-rich zones where the T cells were primarily CD4 + (81%), although CD8+ T cells were also present. The majority of B and T cells expressed germinal center (GC) markers CXCR4, CXCR5, CD40 and CD40L. Moreover, we found a subset of B cells that expressed markers of proliferation and AICDA, suggesting an active GC. We also found that IgA+ plasma cells (PCs) localized to the submucosal glands, such as serous and mucous acini. These cells provide a niche for the IgA+ PCs by expressing TNFSF13 (APRIL), CCL28, FDCSP, and PIGR to transport IgA to the nasal lumen. In summary, we have found that TLFs in the nasal mucosa support humoral immunity. Further studies are warranted to understand their contribution to the IgA+ plasma cell population and in local immunity. Funding Sources This project was funded by the National Institute of Allergies and Infectious Diseases (NIAID) Collaborative Influenza Vaccine Innovation Centers (CIVIC) Contract #75N93019C00051 and the RNA Bioscience Initiative (RBI) Pilot Grants Program. Topic Categories Mucosal and Regional Immunology (MUC)