1. Role of the afferent lymph as an immunological conduit to analyze tissue antigenic and inflammatory load.
- Author
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Nanaware PP, Khan ZN, Clement CC, Shetty M, Mota I, Seltzer ES, Dzieciatkowska M, Gamboni F, D'Alessandro A, Ng C, Nagayama M, Lichti CF, Soni RK, Jacob B Geri, Matei I, Lyden D, Longman R, Lu TT, Wan X, Unanue ER, Stern LJ, and Santambrogio L
- Subjects
- Animals, Mice, Humans, Male, Female, Inflammatory Bowel Diseases immunology, Inflammatory Bowel Diseases pathology, Inflammatory Bowel Diseases metabolism, Dendritic Cells immunology, Dendritic Cells metabolism, Lymph metabolism, Lymph immunology, Inflammation immunology, Inflammation pathology, Inflammation metabolism, Lymph Nodes immunology, Lymph Nodes metabolism, Mice, Inbred C57BL, Antigens metabolism, Antigens immunology
- Abstract
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., Competing Interests: Declaration of interests The authors declare that they do not have any conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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