Small intestine-restricted Th17 enrichment in TSNO mice is associated with increased SFB colonization and ileal epithelial activation
Year: 2026
Type: article
Abstract: Background T helper 17 (Th17) cells are highly enriched in the small intestine and play a critical role in mucosal immunity. Their differentiation is strongly influenced by the gut microbiota, particularly segmented filamentous bacteria (SFB), which induce Th17 responses through interactions with intestinal epithelial cells. In parallel, group 3 innate lymphoid cells (ILC3s) contribute to intestinal immune homeostasis via IL-22-mediated epithelial activation. However, how host genetic background regulates the balance between Th17 cells and ILC3s contributes to region-specific Th17 enrichment remains unclear. Methods We quantified immune cell populations, including Th17 cells, regulatory T cells, and ILC3s, in the small intestinal lamina propria of Tsumura Suzuki nonobese (TSNO), Tsumura Suzuki obese diabetes (TSOD), ddY, and C57BL/6 mice using flow cytometry. SFB abundance was quantified using PCR. Ileal epithelial responses were assessed using immunoblotting and gene expression analyses. To determine microbiota dependence, mice were treated with broad-spectrum antibiotics. Fecal microbiota transplantation (FMT) was performed with germ-free C57BL/6 mice as recipients. Reciprocal TSNO × TSOD F1 progeny were analyzed to assess the contribution of host strain background. Results TSNO mice exhibited markedly greater Th17 cell enrichment in the small intestine than TSOD, ddY, and C57BL/6 mice. Conversely, ILC3 frequency in TSNO mice was reduced, indicating that Th17 dominance does not reflect generalized RORγt + lymphoid population expansion. TSNO mice displayed significantly increased ileal colonization by SFB, accompanied by enhanced epithelial responses, characterized by increased STAT3 phosphorylation and antimicrobial and immune-related gene upregulation. Antibiotic treatment reduced SFB abundance and suppressed Th17-associated gene expression, supporting an association between SFB colonization and the intestinal Th17-associated program. FMT showed that microbiota from TSNO and TSOD mice promoted Th17 responses in germ-free recipients, although the TSNO phenotype was not completely reproduced. Reciprocal TSNO × TSOD F1 progeny exhibited intermediate Th17 cell proportions, supporting an association between host genetic background and the observed phenotype. Conclusions TSNO mice represent a unique model of small intestine-restricted Th17 enrichment associated with increased SFB colonization, enhanced epithelial responsiveness, and strain-associated host factors. Increased SFB colonization may contribute to the early establishment of the Th17-enriched state, whereas host and epithelial factors may contribute to its persistence at later ages.
Source: Inflammation and Regeneration
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,577
OpenAlex ID: W7225718319
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