Bob1+ T follicular helper cells support intestinal mucosal immunity
Abstract
IntroductionThe intestinal environment relies on immunoglobulin A (IgA) produced in mucosa-associated lymphoid tissues, including Peyer’s patches (PPs). While T follicular helper (Tfh) cells are known to facilitate germinal center (GC) formation in PPs, the mechanisms through which Tfh cells regulate IgA production remain unclear. B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator that interacts with octamer-binding transcription factors 1 and 2 (Oct1/2), is notably expressed in Tfh cells and regulates their function during persistent foreign antigen exposure.MethodsTo explore the role of Bob1 in Tfh cells and intestinal immunity, we studied T cell-specific Bob1-deficient mice (CD4Cre/+Bob1fl/fl, FoxP3GFP/DTRCD4Cre/+Bob1fl/fl) alongside control mice (CD4+/+Bob1fl/fl, FoxP3GFP/DTRCD4+/+Bob1fl/fl) under steady-state conditions. We assessed differences in IgA production and subsequently analyzed T and B cell subsets involved in IgA production within the lamina propria (LP) and PPs. Additionally, we examined changes in the intestinal microbial composition in both groups.ResultsFecal IgA levels and the population of IgA+ plasma cells in the small intestinal LP were significantly lower in CD4Cre/+Bob1fl/fl mice than in control CD4+/+Bob1fl/fl mice. Similarly, IgA+ light zone GC B and IgA+ memory B cells were found in reduced populations in PPs of CD4Cre/+Bob1fl/fl mice compared with those in the controls. Furthermore, inducible T-cell costimulator expression was diminished in GC Tfh cells of FoxP3GFP/DTRCD4Cre/+Bob1fl/fl mice compared with that in controls. Analysis of the intestinal microbiota also revealed a reduced abundance of Bacteroidales-associated bacterial populations, including the family Prevotellaceae and Rikenellaceae, in CD4Cre/+Bob1fl/fl mice.ConclusionOur findings indicate that Bob1 is crucial for Tfh cell activation in PPs, which in turn supports intestinal IgA responses and the maintenance of Bacteroidales-associated microbial communities. This study enhances our understanding of the mechanisms underlying intestinal immune responses and lays the groundwork for future research aimed at modulating mucosal immunity.
Related
- HIV remodels germinal centers through T follicular helper cell loss
- Indole induces intestinal T helper-17 cell overproduction during inflammatory bowel disease through PKA/SP1-mediated Trim21 transcription
- A potato late blight pathogen effector interacts with ENTH-domain protein TOL9a and an activated helper NLR to suppress immunity
- Research progress on intestinal probiotics-mediated protection of the intestinal mucosal barrier in ulcerative colitis
- IFN-λ fine tunes protective immunity during mucosal viral infection.
BibTeX
@article{shirato2026bob1,
title = {{Bob1+ T follicular helper cells support intestinal mucosal immunity}},
author = {Shotaro Shirato and Ippei Ikegami and Takashi Sasaki and Ayumi Tatekoshi and Hiroto Horiguchi and Satoshi Iyama and Taiki Sugaya and Masanobu Tanemoto and Takeshi Ohyu and Umi Komabayashi and Masayoshi Kobune and Shingo Ichimiya},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1980099},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1980099},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bob1+ T follicular helper cells support intestinal mucosal immunity
AU - Shotaro Shirato
AU - Ippei Ikegami
AU - Takashi Sasaki
AU - Ayumi Tatekoshi
AU - Hiroto Horiguchi
AU - Satoshi Iyama
AU - Taiki Sugaya
AU - Masanobu Tanemoto
AU - Takeshi Ohyu
AU - Umi Komabayashi
AU - Masayoshi Kobune
AU - Shingo Ichimiya
PY - 2026
DA - 2026/11/04
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1980099
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1980099
AB - IntroductionThe intestinal environment relies on immunoglobulin A (IgA) produced in mucosa-associated lymphoid tissues, including Peyer’s patches (PPs). While T follicular helper (Tfh) cells are known to facilitate germinal center (GC) formation in PPs, the mechanisms through which Tfh cells regulate IgA production remain unclear. B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator that interacts with octamer-binding transcription factors 1 and 2 (Oct1/2), is notably expressed in Tfh cells and regulates their function during persistent foreign antigen exposure.MethodsTo explore the role of Bob1 in Tfh cells and intestinal immunity, we studied T cell-specific Bob1-deficient mice (CD4Cre/+Bob1fl/fl, FoxP3GFP/DTRCD4Cre/+Bob1fl/fl) alongside control mice (CD4+/+Bob1fl/fl, FoxP3GFP/DTRCD4+/+Bob1fl/fl) under steady-state conditions. We assessed differences in IgA production and subsequently analyzed T and B cell subsets involved in IgA production within the lamina propria (LP) and PPs. Additionally, we examined changes in the intestinal microbial composition in both groups.ResultsFecal IgA levels and the population of IgA+ plasma cells in the small intestinal LP were significantly lower in CD4Cre/+Bob1fl/fl mice than in control CD4+/+Bob1fl/fl mice. Similarly, IgA+ light zone GC B and IgA+ memory B cells were found in reduced populations in PPs of CD4Cre/+Bob1fl/fl mice compared with those in the controls. Furthermore, inducible T-cell costimulator expression was diminished in GC Tfh cells of FoxP3GFP/DTRCD4Cre/+Bob1fl/fl mice compared with that in controls. Analysis of the intestinal microbiota also revealed a reduced abundance of Bacteroidales-associated bacterial populations, including the family Prevotellaceae and Rikenellaceae, in CD4Cre/+Bob1fl/fl mice.ConclusionOur findings indicate that Bob1 is crucial for Tfh cell activation in PPs, which in turn supports intestinal IgA responses and the maintenance of Bacteroidales-associated microbial communities. This study enhances our understanding of the mechanisms underlying intestinal immune responses and lays the groundwork for future research aimed at modulating mucosal immunity.
SN - 1664-3224
ER -