Intestinal epithelial cell secretion of RELM-β protects against gastrointestinal worm infection

De'Broski R. Herbert, Jun Qi Yang, Simon P. Hogan, Kathryn Groschwitz, Marat Khodoun, Ariel Munitz, Tatyana Orekov, Charles Perkins, Quan Wang, Frank Brombacher, Joseph F. Urban, Marc E. Rothenberg, Fred D. Finkelman

Research output: Contribution to journalArticlepeer-review


Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) β. RELM-β is essential for normal spontaneous expulsion and IL-4-induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-β is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-β-driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.

Original languageEnglish
Pages (from-to)2947-2957
Number of pages11
JournalJournal of Experimental Medicine
Issue number13
StatePublished - 21 Dec 2009
Externally publishedYes


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