title: Procyanidin B2 gallates inhibit IFN-γ and IL-17 production in T cells by suppressing T-bet and RORγt expression.
abstract: Procyanidins are widely found in plants and have anti-inflammatory activities. Procyanidin B2 (PCB2) inhibits production of proinflammatory cytokines in macrophages. However, there has been no study that has attempted to determine the effects of PCB2 gallates on T cell functions. In the present study, murine splenocytes were isolated and treated with PCB2 or PCB2 gallates in the presence of an anti-CD3 monoclonal antibody (mAb). PCB2 gallates, but not PCB2, inhibited proliferation and T cell activation of splenocytes after stimulation with the anti-CD3 mAb. In addition, PCB2 gallates, particularly 3,3″-di-O-gallate (3,3″-di-OG), significantly inhibited production of interferon (IFN)-γ, interleukin (IL)-12p40, and IL-17 in splenocytes, but did not suppress IL-10 production. Intracellular staining revealed that the expression of IFN-γ and IL-17 in both CD4+and CD8+T cells was obviously decreased by PCB2 3,3″-di-OG compared with PCB2, PCB2 3-OG, and PCB2 3″-OG. Treatment of isolated CD4+and CD8+T cells with procyanidins in the presence of the anti-CD3 mAb led to significant inhibition of IFN-γ production by PCB2 3,3″-di-OG in both cell types. Furthermore, PCB2 3,3″-di-OG suppressed the expression of transcription factors T-bet and RORγt that regulate IFN-γ and IL-17, respectively. In conclusion, we revealed a new mechanism through which PCB2 gallates inhibit IFN-γ and IL-17 production in T cells by down-regulation of T-bet and RORγt expression. Our results suggest that PCB2 gallates have a potential role in Th1/Th17-mediated diseases such as inflammatory and autoimmune diseases.
authors.affiliation: Department of Bioscience and Biotechnology, Graduate School of Agriculture, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan; Frontier Agriscience and Technology Center, Graduate School of Agriculture, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan. Electronic address: tanakasa@shinshu-u.ac.jp.
authors.forename: Sachi
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Bioscience and Biotechnology, Graduate School of Agriculture, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan.
authors.forename: Kanon
authors.initials: K
authors.lastname: Furuya
authors.affiliation: Department of Bioscience and Biotechnology, Graduate School of Agriculture, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Bioscience and Biotechnology, Graduate School of Agriculture, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Graduate School of Agriculture, Sciences of Functional Foods, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Ichikawa
authors.affiliation: Graduate School of Agriculture, Sciences of Functional Foods, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan.
authors.forename: Manato
authors.initials: M
authors.lastname: Suda
authors.affiliation: Graduate School of Agriculture, Sciences of Functional Foods, Shinshu University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Makabe
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D044946:Biflavonoids / Q000627:therapeutic use*; D002392:Catechin / Q000627:therapeutic use*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D044945:Proanthocyanidins / Q000627:therapeutic use*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D000893:Anti-Inflammatory Agents; D044946:Biflavonoids; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D044945:Proanthocyanidins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C479580:procyanidin B2; D007371:Interferon-gamma; D002392:Catechin
keywords: Gallate group; IFN-γ; Procyanidins; T cells; T-bet