Attempts have been made to elucidate the functional markers of regulatory T cells (Tregs), CD4+Foxp3+ T cells with an immunosuppressive function. Sialyl Lewis X (sLex), a tetrasaccharide Ag, is involved in leukocyte trafficking as selectin ligands and is a marker of highly differentiated Tregs in humans. However, the importance of sLex in murine Tregs remains unknown. In this study, we report that sLex defines the activated and functional subset of murine Tregs. The contact hypersensitivity model showed that murine Tregs strongly express sLex upon activation, accompanied by functional Treg marker elevation, such as Foxp3, CD25, CD103, CD39, and granzyme B. RNA sequencing analysis revealed sLex-positive (sLex+) Tregs expressed genes involved in Treg function at a higher level than sLex-negative (sLex-) Tregs. Using an in vitro suppression assay, we found that sLex+ Tregs could more efficiently suppress naive CD4+ T cell proliferation than sLex- Tregs. In the murine contact hypersensitivity elicitation model, the topical sLex+ Treg injection into the ears suppressed ear inflammation more efficiently than that of sLex- Tregs. Our results indicate that sLex could serve as a unique surface marker of activated and functional Tregs with immunosuppressive functions in mice.
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