Background: The small intestinal lamina propria (SiLP) serves as a reservoir for Th17 cells. Although increasing evidence linking intestinal Th17 cells to Rheumatoid Arthritis (RA), the immunological functions of small intestinal CD25 ^low Foxp3 ⁺ T cells and their connection to Th17 cell differentiation and RA pathogenesis remain poorly understood.

Objectives: This study aims to elucidate the immunological characteristics and functional roles of SiLP CD25 ^low Foxp3 ⁺ T cells and their pathogenic involvement in RA development.

Methods: We analyzed CD25 expression in Tregs isolated from PBMCs of RA patients and a mouse model of RA. Treg suppression assays and Th17 differentiation in vitro were conducted using sorted spleen CD25 ^high , CD25 ^low Foxp3 ⁺ T cell and SiLP CD25 ^low Foxp3 ⁺ T cells.

Results: In RA patients, the frequency of CD25 ^low Foxp3 ⁺ T cells was elevated in PBMCs compared to healthy individuals. In normal mice, among Foxp3 ⁺ Tregs from different tissues, CD25 ^low Foxp3 ⁺ T cells were particularly abundant in the small intestinal lamina propria (SiLP). Suppression assays conducted in vitro demonstrated comparable immunosuppressive abilities between spleen-derived CD25 ^high and CD25 ^low Foxp3 ⁺ T cells. However, SiLP CD25 ^low Foxp3 ⁺ T cells displayed diminished capacity to suppress CD4 ⁺ T cell proliferation when compared to their spleen-derived counterparts. Th17 differentiation experiments highlighted a higher propensity of SiLP CD25 ^low Foxp3 ⁺ T cells to adopt a Th17-like phenotype relative to spleen CD25 ^high Foxp3 ⁺ and CD25 ^low Foxp3 ⁺ T cells. Moreover, under Th17-skewing conditions, SiLP CD25 ^low Foxp3 ⁺ T cells produced significantly more IL-17A compared to spleen-derived Foxp3 ⁺ T cells.

Conclusion: Our results indicate that SiLP CD25 ^low Foxp3 ⁺ T cells contribute to disease pathogenesis. Gaining a more comprehensive understanding of these cells may shed light on the mechanisms driving Treg cell plasticity and pave the way for therapeutic strategies aimed at modulating their function.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.