Role of the afferent lymph as an immunological conduit to analyze tissue antigenic and inflammatory load

The lymphatic fluid is the conduit by which part of the tissue “omics” is transported to the draining lymph node for immunosurveillance. Following cannulation of the pre-nodal cervical and mesenteric afferent lymphatics, herein we investigate the lymph proteomic composition, uncovering that its composition varies according to the tissue of origin. Tissue specificity is also reflected in the dendritic cell-major histocompatibility complex class II-eluted immunopeptidome harvested from the cervical and mesenteric nodes. Following inflammatory disruption of the gut barrier, the lymph antigenic and inflammatory loads are analyzed in both mice and subjects with inflammatory bowel diseases. Gastrointestinal tissue damage reflects the lymph inflammatory and damage-associated molecular pattern signatures, microbiome-derived by-products, and immunomodulatory molecules, including metabolites of the gut-brain axis, mapped in the afferent mesenteric lymph. Our data point to the relevance of the lymphatic fluid to probe the tissue-specific antigenic and inflammatory load transported to the draining lymph node for immunosurveillance. [Display omitted] •The cervical and mesenteric afferent lymph carries an “omic” tissue-specific signature•This signature is reflected in the draining nodes’ dendritic cell-MHC-II immunopeptidome•The lymph has a pivotal role in organ-specific immunosurveillance Nanaware et al. report the tissue-specific composition of the cervical and mesenteric lymph in physiological and inflammatory conditions in subjects with inflammatory bowel diseases and a mouse model. The tissue specificity is mirrored in the nodal dendritic cell-MHC-II immunopeptidome, including microbiome-related peptides. The analysis showcases the lymph’s crucial role in immunosurveillance.