Role of the afferent lymph as an immunological conduit to analyze tissue antigenic and inflammatory load
Padma P. Nanaware,
Zohaib N. Khan,
Cristina C. Clement,
Madhur Shetty,
Ines Mota,
Ethan S. Seltzer,
Monika Dzieciatkowska,
Fabia Gamboni,
Angelo D’Alessandro,
Charles Ng,
Manabu Nagayama,
Cheryl F. Lichti,
Rajesh K. Soni,
Jacob B. Geri,
Irina Matei,
David Lyden,
Randy Longman,
Theresa T. Lu,
Xiaoxiao Wan,
Emil R. Unanue,
Lawrence J. Stern,
Laura Santambrogio
Affiliations
Padma P. Nanaware
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Zohaib N. Khan
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA
Cristina C. Clement
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA
Madhur Shetty
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA
Ines Mota
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA
Ethan S. Seltzer
Pediatric Rheumatology and Autoimmunity and Inflammation Program, Hospital for Special Surgery Research Institute, New York NY 100021, USA
Monika Dzieciatkowska
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Fabia Gamboni
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Angelo D’Alessandro
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Charles Ng
Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, NY 10065, USA
Manabu Nagayama
Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, NY 10065, USA
Cheryl F. Lichti
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
Rajesh K. Soni
Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York 10032, NY, USA
Jacob B. Geri
Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics and Cell and Developmental Biology, Drukier Institute for Children’s Health, Weill Cornell Medicine, New York, NY 10065, USA
Irina Matei
Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics and Cell and Developmental Biology, Drukier Institute for Children’s Health, Weill Cornell Medicine, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, New York, NY 10065, USA
David Lyden
Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics and Cell and Developmental Biology, Drukier Institute for Children’s Health, Weill Cornell Medicine, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, New York, NY 10065, USA
Randy Longman
Division of Gastroenterology and Hepatology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, NY 10065, USA
Theresa T. Lu
Pediatric Rheumatology and Autoimmunity and Inflammation Program, Hospital for Special Surgery Research Institute, New York NY 100021, USA
Xiaoxiao Wan
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
Emil R. Unanue
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
Lawrence J. Stern
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Laura Santambrogio
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, New York, NY 10065, USA; Caryl and Israel Englander Institute for Precision Medicine, New York, NY 10065, USA; Corresponding author
Summary: 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.
