Role of CCL28 for mucosal immunity

• Project/Area Number: 26460582
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Kindai University
• Principal Investigator: YOSHIE Osamu 近畿大学, 医学部, 教授 (10166910)
• Co-Investigator(Kenkyū-buntansha): 樋口 智紀 高知大学, 教育研究部医療学系基礎医学部門, 助教 (00448771) ; 金井 亨輔 近畿大学, 医学部, 助教 (20596621) ; 藤田 貢 近畿大学, 医学部, 准教授 (40609997)
• Co-Investigator(Renkei-kenkyūsha): NAKAYAMA Takashi 近畿大学, 薬学部, 教授 (60319663)
• Research Collaborator: TSUNODA Ikuo 近畿大学, 医学部, 教授 (00261529)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ケモカイン / CCL28 / 腸管免疫 / IgA / 腸内細菌叢 / 腸管マイクロビオーム / IgA 産生細胞 / 粘膜免疫 / 抗菌作用 / CCR10 / 腸管細菌叢 / IgA産生細胞 / 好酸球

Outline of Final Research Achievements

CCL28 is expressed in the mucosal tissues and to attract IgA-antibody secreting cells (IgA-ASCs) via CCR10. CCL28 has an antimicrobial activity against microbes in vitro. However, in vivo evidence for the role of CCL28 in the mucosal immunity remains scanty. We generated CCL28-deficient mice and demonstrated that CCL28-deficient mice showed reduced numbers and altered distribution of IgA-ASCs in the colon. The IgA contents in the fecal extracts were low. The average amounts of IgA secreted by a single IgA-ASC isolated from the lamina propria of the colon was reduced. Furthermore, the 16S rRNA sequencing analysis of feces revealed an increase of the Class Bacilli. Consistent with the low IgA production and altered microbiota in the colon, CCL28-deficient mice had aggravated colitis upon treatment with dextran sulfate, which was ameliorated by oral antibiotics. Therefore, CCL28 has an role in the mucosal immunity of the colon as a chemoattractant with a direct antimicrobial activity.

Research Products

• [Journal Article] IL-35 suppresses lipopolysaccharide-induced airway eosinophilia in EBI3-deficient mice. (2017)
  • Author(s): Kanai K, Park AM, Yoshida H, Tsunoda I, Yoshie O.
  • Journal Title: Journal of Immunology Volume: 198(1) Issue: 1 Pages: 119-127
  • DOI: 10.4049/jimmunol.1600506
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Upregulated CCL28 expression in the nasal mucosa in experimental allergic rhinitis: Implication for CD4(+) memory T cell recruitment (2016)
  • Author(s): Nagakubo D, Yoshie O, Hirata T
  • Journal Title: Cellular Immunology Volume: 302 Pages: 58-62
  • DOI: 10.1016/j.cellimm.2016.02.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CCR4 and its ligands: from bench to bedside (2015)
  • Author(s): Yoshie O, Matsushima K
  • Journal Title: International Immunology Volume: 27 Issue: 1 Pages: 11-20
  • DOI: 10.1093/intimm/dxu079
  • Peer Reviewed
• [Journal Article] Functional roles of evolutionary conserved motifs and residues in vertebrate chemokine receptors (2015)
  • Author(s): Nomiyama H, Yoshie O
  • Journal Title: Journal of Leukocyte Biology Volume: 97 Issue: 1 Pages: 39-47
  • DOI: 10.1189/jlb.2ru0614-290r
  • Peer Reviewed
• [Journal Article] Generation of colonic IgA-secreting cells in the cecal patch (2014)
  • Author(s): Masahata, K., Umemoto, E., Kayama, H., Kotani, M., Nakamura, S., Kurakawa, T., Kikuta, J., Gotoh, K., Motooka, D., Sato, S., Higuchi, T., Baba, Y., Kurosaki, T., Kinoshita, M., Shimada, Y., Kimura, T., Okumura, R., Takeda, A., Tajima, M., Yoshie, O., Fukuzawa, M., Kiyono, H., Fagarasan, S., Iida, T., Ishii, M., Takeda, K
  • Journal Title: Nature Comm Volume: 5 Issue: 1 Pages: 3704-3704
  • DOI: 10.1038/ncomms4704
  • Peer Reviewed / Open Access
• [Presentation] ケモカインCCL28の欠損はDSS腸炎モデルマウスにおける病態を増悪させる (2017)
  • Author(s): 神原弘和、松尾一彦、山本真也、長久保大輔、義江 修、中山隆志
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
  • Year and Date: 2017-03-25
• [Presentation] CCL28 plays an intestinal protection against microbes in vivo as a chemoattractant for IgA-secreting cells and also as an antimicrobial activity. (2015)
  • Author(s): Matsuo K, Fujita M, Nakayaa T, Yoshie O.
  • Organizer: 第 44 回日本免疫学会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18
• [Presentation] ケモカイン MEC/CCL28 の腸管組織における生物学的役割 (2015)
  • Author(s): 松尾一彦、 北田卓也、重田暁子、藤田貢、義江修、中山隆志
  • Organizer: 日本薬学会第 135 年会
  • Place of Presentation: 神戸学院大学 (神戸市)
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] ケモカイン MEC/CCL28 は IgA 抗体産生細胞の腸管組織への遊走を制御することで DSS 誘発性大腸炎の劇症化抑制に寄与する (2014)
  • Author(s): 北田卓也、松尾一彦、重田 暁子、藤田貢、義江修、中山隆志
  • Organizer: 生体機能と創薬シンポジウム 2014
  • Place of Presentation: 近畿大学 (東大阪市)
  • Year and Date: 2014-08-28 – 2014-08-29