The Wnt inhibitor secreted Frizzled‐Related Protein 1 (sFRP1) promotes human Th17 differentiation |
| |
Authors: | Yoon‐Sook Lee Kyoo‐A Lee Hae‐Bom Yoon Seung‐Ah Yoo Young Woo Park Yeonseok Chung Wan‐Uk Kim Chang‐Yuil Kang |
| |
Institution: | 1. Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, , Seoul, Korea;2. Department of Internal Medicine, Division of Rheumatology, School of Medicine, Catholic University of Korea, , Seoul, Korea;3. Integrative Omics Research Center, Korea Research Institute of Bioscience and Biotechnology, , Daejeon, Korea;4. Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, The University of Texas‐Health Science Center at Houston, , Houston, TX, USA;5. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, , Seoul, Korea |
| |
Abstract: | Wnt/β‐catenin signaling plays a crucial role during embryogenesis and tumorigenesis, and in T cells, promotes the differentiation of Th2 cells. However, the role of Wnt signals in the differentiation and maintenance of human Th17 cells remains poorly understood. We found that the higher levels of IL‐17 in the synovial fluid of rheumatoid arthritis (RA) patients compared with that of osteoarthritis (OA) patients were associated with a higher concentration of sFRP1 (secreted Frizzled‐Related Protein 1), an inhibitor of the Wnt/β‐catenin pathway. The addition of sFRP1 during TCR‐mediated stimulation induced a significant increase in IL‐17 production by both naïve and memory CD4+ T cells. Moreover, under Th17‐differentiation conditions, the addition of sFRP1 significantly reduced the requirement for TGF‐β. Mechanistically, we observed that sFRP1 significantly enhanced the phosphorylation of Smad2/3 in CD4+ T cells upon TGF‐β stimulation and that blocking TGF‐β signaling abolished the Th17‐promoting activity of sFRP1. Our findings reveal a novel function for sFRP1 as a potent inducer of human Th17‐cell differentiation. Consequently, sFRP1 may represent a promising target for the treatment of Th17‐mediated disease in humans. |
| |
Keywords: | Differentiation Secreted Frizzled‐Related Protein 1 Th17 cells Wnt |
|
|