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UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE.
Liu, Limin; Hu, Longyuan; Yang, Linxuan; Jia, Sujie; Du, Pei; Min, Xiaoli; Wu, Jiali; Wu, Haijing; Long, Hai; Lu, Qianjin; Zhao, Ming.
Afiliación
  • Liu L; Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
  • Hu L; Research Unit of Key Technologies of Diagnosis and Treatment for Immune-Related Skin Diseases, Chinese Academy of Medical Sciences (2019RU027), Changsha, Hunan, China.
  • Yang L; Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
  • Jia S; Research Unit of Key Technologies of Diagnosis and Treatment for Immune-Related Skin Diseases, Chinese Academy of Medical Sciences (2019RU027), Changsha, Hunan, China.
  • Du P; Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
  • Min X; Research Unit of Key Technologies of Diagnosis and Treatment for Immune-Related Skin Diseases, Chinese Academy of Medical Sciences (2019RU027), Changsha, Hunan, China.
  • Wu J; Department of Pharmacy, Central South University, The Third Xiangya Hospital, Changsha, China.
  • Wu H; Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
  • Long H; Research Unit of Key Technologies of Diagnosis and Treatment for Immune-Related Skin Diseases, Chinese Academy of Medical Sciences (2019RU027), Changsha, Hunan, China.
  • Lu Q; Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
  • Zhao M; Research Unit of Key Technologies of Diagnosis and Treatment for Immune-Related Skin Diseases, Chinese Academy of Medical Sciences (2019RU027), Changsha, Hunan, China.
Clin Epigenetics ; 13(1): 31, 2021 02 10.
Article en En | MEDLINE | ID: mdl-33568199
BACKGROUND: Transcription factor B cell lymphoma 6 (BCL6) is a master regulator of T follicular helper (Tfh) cells, which play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanisms by which BCL6 expression is regulated are poorly understood. Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important epigenetic factor that regulates DNA methylation and histone modifications. In the present study, we assessed whether UHRF1 can regulate BCL6 expression and influence the differentiation and proliferation of Tfh cells. RESULTS: Compared to healthy controls, the mean fluorescence intensity of UHRF1 (UHRF1-MFI) in Tfh cells from SLE patients was significantly downregulated, whereas that of BCL6 (BCL6-MFI) was significantly upregulated. In vitro, UHRF1 knockdown led to BCL6 overexpression and promoted Tfh cell differentiation. In contrast, UHRF1 overexpression led to BCL6 downregulation and decreased Tfh cell differentiation. In vivo, conditional UHRF1 gene knockout (UHRF1-cKO) in mouse T cells revealed that UHRF1 depletion can enhance the proportion of Tfh cells and induce an augmented GC reaction in mice treated with NP-keyhole limpet hemocyanin (NP-KLH). Mechanistically, UHRF1 downregulation can decrease DNA methylation and H3K27 trimethylation (H3K27me3) levels in the BCL6 promoter region of Tfh cells. CONCLUSIONS: Our results demonstrated that UHRF1 downregulation leads to increased BCL6 expression by decreasing DNA methylation and H3K27me3 levels, promoting Tfh cell differentiation in vitro and in vivo. This finding reveals the role of UHRF1 in regulating Tfh cell differentiation and provides a potential target for SLE therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Proteínas Potenciadoras de Unión a CCAAT / Ubiquitina-Proteína Ligasas / Proteínas Proto-Oncogénicas c-bcl-6 / Células T Auxiliares Foliculares / Lupus Eritematoso Sistémico Límite: Animals / Female / Humans / Male Idioma: En Revista: Clin Epigenetics Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Proteínas Potenciadoras de Unión a CCAAT / Ubiquitina-Proteína Ligasas / Proteínas Proto-Oncogénicas c-bcl-6 / Células T Auxiliares Foliculares / Lupus Eritematoso Sistémico Límite: Animals / Female / Humans / Male Idioma: En Revista: Clin Epigenetics Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania