Distinct roles for B cell-derived LTα3 and LTα1β2 in TNF-mediated ileitis.

ABSTRACT: Crohn's disease pathology is modeled in TNF^ΔARE+/- mice that overproduce tumor necrosis factor (TNF) to drive disease through TNF receptors. An alternative ligand for TNF receptors, soluble LTα₃, is produced by B cells, but has received scarce attention because LTα also partners with LTβ to generate membrane-tethered LTαβ₂ that promotes tertiary lymphoid tissue-another feature of Crohn's disease. We hypothesized that B cell-derived LTαβ₂ would critically affect ileitis in TNF^ΔARE+/- mice. However, whereas deleting LTβ in B cells was essential for tertiary lymphoid tissue, disease pathology was minimally affected. By contrast, loss of B cell-derived LTα increased intestinal permeability, shrunk the pool of IgA⁺ ileal plasma c

SUBMITTER: Erlich EC 

PROVIDER: S-EPMC12479355 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature