Immune quiescence in the oral mucosa is maintained by a uniquely large population of highly activated Foxp3+ regulatory T cells




The oral mucosa is a critical barrier tissue that protects the oral cavity against invading pathogens and foreign antigens. Interestingly, inflammation in the oral cavity is rarely observed, indicating that overt immune activation in this site is actively suppressed. Whether Foxp3+ Treg cells are involved in controlling immunity of the oral mucosa, however, is not fully understood. Here, we show that the oral mucosa is highly enriched in Foxp3+ Treg cells, and that oral mucosa Treg cells are phenotypically distinct from those of LN or spleen, as they expressed copious amounts of the tissue-retention molecule CD103 and unusually high-levels of CTLA4. Acute depletion of Foxp3+ Treg cells had catastrophic effects, resulting in marked infiltration of activated effector T cells that were associated with autoimmunity and tissue destruction of the oral mucosa. Moreover, adoptive transfer of naive CD4 T cells revealed that the oral mucosa is highly ineffective in inducing Foxp3+ Treg cells in situ, so that it depends on recruitment and migration of exogenous Treg cells to populate this mucosal site. Collectively, these results demonstrate a previously unappreciated role and a distinct developmental pathway for Foxp3+ Treg cells in the oral mucosa, which are essential to control local tissue immunity.

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We thank Dr. A. Singer for critical review of this manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.

Author information


  1. Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    • Joo-Young Park
    • , Hyunsoo Chung
    • , Devon T. DiPalma
    • , Xuguang Tai
    •  & Jung-Hyun Park
  2. Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, 101 Daehakno, Jongno-gu, Seoul, 03080, South Korea

    • Joo-Young Park


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J.-Y.P. designed the study, performed and analyzed experiments, prepared figures, and wrote the manuscript; H.C., D.T.D., and X.T. performed experiments and analyzed data; J.-H.P. directed the study, analyzed data, and wrote the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Joo-Young Park or Jung-Hyun Park.

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