title: Increased expression of TLR2 in CD4(+) T cells from SLE patients enhances immune reactivity and promotes IL-17 expression through histone modifications.
abstract: The innate immune system has been shown to play an important pathologic role in systemic lupus erythematosus (SLE). TLR2, a PRR, recognizes exogenous PAMPs, and endogenous damage-associated molecular patterns and has been implicated in the initiation and maintenance of the perpetuated inflammatory reactions in autoimmune diseases. Here, we report increased expression of TLR2 in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes from SLE patients. Conventional treatment, such as hydroxychloroquine and corticosteroids, showed no effect on TLR2 expression in CD4(+) T cells from SLE patients. In vitro stimulation of TLR2 in CD4(+) T cells from SLE patients increased CD40L and CD70 expression, as well as secretion of IL-6, IL-17A, IL-17F, and TNF-α, while Foxp3 transcription decreased. This effect was reversed by TLR2 siRNA. Moreover, TLR2 activation upregulated H3K4 tri-methylation and H4 acetylation levels while downregulated H3K9 tri-methylation level in the IL-17A promoter region. In addition, it also increased H4 acetylation levels and decreased H3K9 tri-methylation levels in the IL-17F promoter region. In summary, our findings demonstrate that increased expression of TLR2 contributes to immune reactivity and promotes IL-17A and IL-17F expression through histone modifications in SLE.
authors.affiliation: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, P. R. China.
authors.forename: Jieyue
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, P. R. China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Susan
authors.initials: S
authors.lastname: Yung
authors.affiliation: Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, P. R. China.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053282:CD27 Ligand / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006657:Histones / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology
chemical_list: D053282:CD27 Ligand; C505771:CD70 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006657:Histones; C508717:IL17A protein, human; C440021:IL17F protein, human; D020381:Interleukin-17; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D023201:CD40 Ligand
keywords: Histone modification; IL-17; Systemic lupus erythematosus; T cells; TLR2