MLL1 directs gut-associated antibody responses to helminth and bacterial infections

Zhang, Y; Chakma, C; Kirn, A; Chisanga, D; Polmear, J; Zaini, A; Farighi, R; Dalit, L; Xie, L; L&#243;pez-Ure&#241;a, D; Mileto, S; Lyras, D; Zaph, C; Groom, JR; Good-Jacobson, KL

Author(s): Zhang, Y; Chakma, C; Kirn, A; Chisanga, D; Polmear, J; Zaini, A; Farighi, R; Dalit, L; Xie, L; López-Ureña, D; Mileto, S; Lyras, D; Zaph, C; Groom, JR; Good-Jacobson, KL;
Details: Publication Year 2026-02-09,Volume 215,Issue #2,Page vkaf358
Journal Title: Journal of Immunology
Abstract: Soil-transmitted helminths are one of the most common infections globally, yet how to promote effective gut-associated humoral responses is not well understood. We identify the histone methyltransferase MLL1 as a key target to promote IgA-driven responses. Mll1 was increased in germinal center B cells in gut-associated lymphoid tissues, and Mll1-deficiency led to changes in the histone modification H3K4me3 on key B cell and immune-regulatory genes. Correspondingly, MLL1-deficient B cells had defective germinal centers and IgG1 in response to the helminth Trichuris muris. Yet Mll1f/fCd23cre/+ mice expelled worms more rapidly compared to control mice. Accelerated worm clearance correlated with elevated immunoglobulin A (IgA)+ plasma cells, as well as both serum and fecal IgA. RNA-sequencing identified CCR9 as a key MLL1-regulated molecule. As such, Mll1f/fCd23cre/+ mice infected with T. muris had increased IgA+CCR9+ PC localized in the large intestine. Regulation of IgA by MLL1 was confirmed beyond T. muris infection. In vitro cultures confirmed Mll1-deficiency increased IgA+ plasma cells in a B cell-intrinsic manner, and IgA production was also increased in Mll1f/fCd23cre/+ mice infected with the bacterium Citrobacter rodentium. This study reveals MLL1 as a key target to promote IgA responses to gut-associated infections.
Publisher: Oxford Academic
Keywords: B cells; IgA; Mll1; epigenetics; gut-associated lymphoid tissue
Research Division(s): Immunology
PubMed ID: 41764736
Publisher's Version: https://doi.org/ 10.1093/jimmun/vkaf358
Open Access at Publisher's Site: https://doi.org/10.1093/jimmun/vkaf358.
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-03-16 01:38:21

Last Modified: 2026-03-16 01:52:35