Spp1+ macrophages enhance regulatory T cells recruitment and infiltration to alleviate DSS-induced colitis

Objective: Macrophages are essential regulators of intestinal homeostasis by managing gut inflammation and facilitating wound repair. Spp1+ macrophages are involved in chronic inflammation across various organs. This study aims to investigate the role of Spp1+ macrophages in regulating inflammatory responses and tissue remodeling during DSS-induced colitis. Methods: We employed single-cell RNA sequencing to analyze the characteristics of Spp1+ macrophages and used Spp1-tdTomato reporter mice to track their localization and dynamics in vivo. Additionally, we utilized a mouse model to specifically ablate Spp1 expressing myeloid cells, enabling us to assess the functional role of these macrophages in DSS-induced colitis. Results: Spp1+ macrophages were characterized by the expression of various chemokines and cytokines. Their numbers significantly expanded as DSS-induced colitis progressed and persisted into the late recovery phase. Depletion of Spp1+ macrophages exacerbated disease severity, particularly during the recovery phase. Moreover, the depletion led to a marked reduction in the percentage of colonic CD4+ T cells, particularly T-bet+ regulatory T (Treg) cells during DSS-induced colitis. Conclusion: Spp1+ macrophages are essential for controlling inflammation and immune responses during DSS-induced colitis by regulating T cell recruitment and infiltration. Targeting Spp1+ macrophages could provide a promising therapeutic strategy for treating gut inflammation. This research was funded by grant R01AI162791 from NIH. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.