Adipose-mesenchymal stromal cells suppress experimental Sjögren syndrome by IL-33-driven expansion of ST2+ regulatory T cells
Ousheng Liu,
Junji Xu,
Fu Wang,
Wenwen Jin,
Peter Zanvit,
Dandan Wang,
Nathan Goldberg,
Alexander Cain,
Nancy Guo,
Yichen Han,
Andrew Bynum,
Guowu Ma,
Songlin Wang,
Zhangui Tang,
Wanjun Chen
Affiliations
Ousheng Liu
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA; Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha 410008, China
Junji Xu
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Fu Wang
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA; Dalian Medical University, School of Stomatology, Dalian 116044, China
Wenwen Jin
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Peter Zanvit
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Dandan Wang
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Nathan Goldberg
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Alexander Cain
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Nancy Guo
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Yichen Han
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Andrew Bynum
Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA
Guowu Ma
Dalian Medical University, School of Stomatology, Dalian 116044, China
Songlin Wang
Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing 100050, China
Zhangui Tang
Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha 410008, China
Summary: Adipose-derived mesenchymal stromal cells (ADSCs) play important roles in the alleviation of inflammation and autoimmune diseases. Interleukin-33 (IL-33), a member of the IL-1 family, has been shown to regulate innate and adaptive immunity. However, it is still unknown whether ADSCs regulate immune responses via IL-33. We show here that ADSCs produced IL-33 in response to IL-1β stimulation, which depended on TAK1, ERK, and p38 pathways. ADSCs-derived IL-33 drove the proliferation of CD4+Foxp3+ST2+ regulatory T cells (Tregs) and alleviated experimental autoimmune Sjögren syndrome in mice. Importantly, human ADSCs also produced IL-33 in response to IL-1β. Thus, we have revealed a previously unrecognized immunoregulatory function of ADSCs by IL-33 production in experimental autoimmunity, which may have clinical applications for human immunopathology.
