Distinct roles for B cell-derived LTα3 and LTα1β2 in TNF-mediated ileitis
Year: 2025
Type: article
Abstract: B lymphocytes may facilitate chronic inflammation through antibody production or secretion of cytokines, including lymphotoxin (LT)-a1b2 associated with development of lymphoid tissue. Tertiary lymphoid structures (TLS) characterize human and murine ileitis by suppressing outflow from the ileum. Here, we show that B cell-derived secretory IgA protected against ileal inflammation, whereas B cell-derived LTa guarded against ileitis-associated loss of body mass. We initially hypothesized this protection resulted from formation of TLS that suppressed lymphatic outflow and thereby restrained systemic spread of inflammatory signals, but B cell-selective deletion of LTb did not exacerbate weight loss, despite eliminating TLS. Instead, weight loss driven by the cachectic cytokine TNF was exacerbated when LTa3, another ligand for TNF receptors, was selectively neutralized. Thus, B cells’ multi-faceted impact on ileitis includes generating secretory IgA, expressing LTa1b2 to drive formation of TLS, and producing LTa3 for protecting against weight loss in the presence of TNF.
Source: Nature Immunology
Authors: Emma C. Erlich, Quazim A. Alayo, Ayoung Kim, Jichang Han, Rachel L. Mintz, Christopher G. Huckstep, Heather S. Ruiz, Rachael L. Field, Taylor J. Dunning, Leila S. Saleh, Mark H. Hoofnagle, Alexei V. Tumanov, Farshid Guilak, Jonathan R. Brestoff, Rafael S. Czepielewski, Gwendalyn J. Randolph
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: U.S. Department of Health and Human Services, Burroughs Wellcome Fund, Cancer Prevention and Research Institute of Texas, American Gastroenterological Association, Crohn's and Colitis Foundation, National Institute on Aging, NIH Office of the Director, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Awards: G1556949721, G1685029277, G2902285999, G3248334371, G4173996564, G4682828459, G4823702983, G5619035416, G5641612780, G5678395754, G5926031272, Overcoming liver toxicity of anti-CD137 cancer immunotherapy, G631042340, Training African giant rats as a cheap diagnostic tool for early TB detection, G8026695365, G8408894234, G8475055495, G8769492301, G8913708126, G8943181901, Gut region-specific mechanisms that limit dissemination of microbial signals from the intestine, Washington University Nutrition Obesity Research Center, Neuroimmunology of AD and CAA with focus on innate immunity and lymphatics, The Cleveland Digestive Diseases Research Core Center (DDRCC), Washington University Rheumatic Diseases Research Resource-based Center, Pediatric Gastroenterology Research Training Program, Mechanisms Underlying the Omental Support of Ovarian Cancer Peritoneal Metastasis, Deciphering the role of tumor-macrophage crosstalk during metastatic dissemination to the peritoneum, RESOURCE BASED CENTER FOR MUSCULOSKELETAL BIOLOGY AND MEDICINE, Defining the lymphatic basis of protein losing enteropathy after Fontan palliation or inflammatory gut disease, Intestinally restricted LXR agonism in ameliorating liver failure in short gut syndrome, Clinical/Laboratory Training Academic Gastroenterology, Differentiation and Function of Monocytes and Macrophages, Training Program in Basic Immunology, Mechanisms that alter lymphatic transport in inflammatory bowel disease, Cancer Center Support Grant, Host-environment interactions in the pathophysiology of digestive disease, Skeletal Disorders Training Program, Immunobiology of the Rheumatic Diseases
OpenAlex ID: W4414064860