The regulation of humoral immune responses mediated by apoptotic cells clearance of follicular dendritic cells

• Project/Area Number: 26670185
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: University of Tsukuba
• Principal Investigator: Honda Shinichiro 筑波大学, 医学医療系, 研究員 (60360640)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 濾胞樹状細胞 / アポトーシス / 胚中心形成 / 液性免疫応答

Outline of Final Research Achievements

Follicular dendritic cells (FDCs) locate within the follicules of lymphoid tissues and are the critical cells for the germinal center formation and humoral immune responses. By using novel isolation method for FDCs, we observed that FDCs engulf apoptotic cells via interaction between self-producing MFG-E8 and αV integrin. We also observed that IL-6 and CXCL-13 production by FDCs are regulated by the engulfment of apoptotic cells. Although we established mice whose αV integrin expression is specifically ablated on FDCs (FDCs-specific αV integrin null mice), germinal center formation and humoral immune responses seems to be comparable between FDCs-specific αV integrin null mice and control mice.

Research Products

• [Journal Article] IgM-Dependent Phagocytosis in Microglia Is Mediated by Complement Receptor 3, Not Fcα/μ Receptor (2015)
  • Author(s): Weinstein JR, Quan Y, Hanson JF, Colonna L, Iorga M, Honda S, Shibuya K, Shibuya A, Elkon KB, Möller T.
  • Journal Title: J Immunol Volume: 195(11) Issue: 11 Pages: 5309-5317
  • DOI: 10.4049/jimmunol.1401195
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immune regulation by Fcα/μ receptor (CD351) on marginal zone B cells and follicular dendritic cells (2015)
  • Author(s): Shibuya A, Honda S.
  • Journal Title: Immunol Rev Volume: 268(1) Issue: 1 Pages: 288-295
  • DOI: 10.1111/imr.12345
  • Peer Reviewed
• [Journal Article] CD155 (PVR/Necl5) Mediates a Costimulatory Signal in CD4+ T Cells and Regulates Allergic Inflammation (2015)
  • Author(s): 4.Yamashita--Kanemaru Y, Takahashi Y, Wang Y, Tahara-Hanaoka S, Honda S, Bernhardt G, Shibuya A, Shibuya K.
  • Journal Title: J Immunol, 194(12):5644-5653, 2015 Volume: 194 Issue: 12 Pages: 5644-5653
  • DOI: 10.4049/jimmunol.1401942
  • Peer Reviewed / Open Access
• [Journal Article] Increased serum IgA in Fcα/μR-deficient mice on the (129 x C57BL/6) F1 genetic background (2015)
  • Author(s): Kurita N, Honda S, Shibuya A.
  • Journal Title: Mol Immunol Volume: 63 Issue: 2 Pages: 367-372
  • DOI: 10.1016/j.molimm.2014.09.008
  • NAID: 120007136500
  • Peer Reviewed / Open Access
• [Journal Article] Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated infammatory monocyte migration (2014)
  • Author(s): Naoya T otsuka, Yun-Gi Kim, Kazumasa Kanemaru, Kouta Niizuma, Eiji Umemoto, Kei Nagai, Satoko T ahara-Hanaoka, Chigusa Nakahasi-Oda, Shin-ichiro Honda, Masayuki Miyasaka, Kazuko Shibuya & Akira Shibuya
  • Journal Title: Nature Communications Volume: 5:4710 Issue: 1 Pages: 4710-4710
  • DOI: 10.1038/ncomms5710
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum under-O-glycosylated IgA1 level is not correlated with glomerular IgA deposition based upon heterogeneity in the composition of immune complexes in IgA nephropathy. (2014)
  • Author(s): Satake K, Shimizu Y, Sasaki Y, Yanagawa H, Suzuki H, Suzuki Y, Horikoshi S, Honda S, Shibuya K, Shibuya A, Tomino Y.
  • Journal Title: BMC Nephrology Volume: 15:89 Issue: 1 Pages: 89-89
  • DOI: 10.1186/1471-2369-15-89
  • Peer Reviewed / Open Access
• [Presentation] Development of a novel method for isolation of follicular dendritic cells (2015)
  • Author(s): Sato K, Honda S, Shibuya K, Shibuya A.
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-19
• [Presentation] Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signaling (2015)
  • Author(s): Honda S, Sato K, Totsuka N, Fujiyama S, Fujimoto M, Miyake K, Nakahashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A.
  • Organizer: International Symposium on Immune Regulation
  • Place of Presentation: Oarai Park Hotel, Ibaraki
  • Year and Date: 2015-10-29
• [Presentation] Marginal zone B cells exacerbate endotoxin shock by secretion of interleukin-6. (2014)
  • Author(s): Honda S, Sato K, Fujiyama S, Fujimoto M, Miyake K, Shibuya A
  • Organizer: 第43 回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-10
• [Presentation] Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration (2014)
  • Author(s): Totsuka N, Kim YG, Kanemaru K, Niizuma K, Umemoto E, Nagai K, Tahara-Hanaoka S, Nakahashi-Oda C, Honda S, Miyasaka M, Shibuya K, Shibuya A.
  • Organizer: 第43 回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-10
• [Remarks] 免疫学研究室ホームページ
  • URL: http://immuno-tsukuba.com/index.html
• [Remarks] つくばリポジトリ
  • URL: https://tsukuba.repo.nii.ac.jp/index.php?action=pages_view_main&active_action=repository_view_main_item_snippet&index_id=984&pn=1&count=20&order=7&lang=japanese&page_id=13&block_id=83
• [Remarks] 筑波大学 免疫学研究室 業績
  • URL: http://immuno-tsukuba.com/publication/english.html
• [Remarks] つくばリポジトリ
  • URL: http://www.tulips.tsukuba.ac.jp/dspace/simple-search?query=%E6%9C%AC%E5%A4%9A+%E4%BC%B8%E4%B8%80%E9%83%8E