Regulation of epithelial barrier by innate lymphoid cell and TLR

• Project/Area Number: 18K08268
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Tottori University
• Principal Investigator: Sugita Kazunari 鳥取大学, 医学部附属病院, 准教授 (40412647)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: バリア学 / 自然リンパ球 / ケラチノサイト

Outline of Final Research Achievements

Type 2 innate lymphoid cells (ILC2s) have been shown to be involved in allergic diseases, such as asthma and atopic dermatitis. We explored the role of ILC2s in the regulation of the epithelial barrier by employing keratinocytes. Cocultures of epithelial cells and ILC2s were used to measure barrier integrity and determine transepithelial resistance and paracellular macromolecule passage. Coculture of keratinocytes with ILC2s revealed a significant decrease in transepithelial resistance. However, addition of TLR (Toll-like receptor)ligand in ILC2 cocultures with keratinocytes restored the barrier function. These data demonstrate that ILC2 and TLR may play a role in keratinocytes.

Academic Significance and Societal Importance of the Research Achievements

ILCが自然免疫に関与するTLRやTLRリガンドとの関連については明らかにされていなかった。本研究はアレルギー炎症のイニシエーターエフェクターであるILCのバリアを制御する機構を解明するとともに、TLRを介したILCによるバリア制御機構の一端を明らかにした点が意義のあることであると考えられる。本研究は、ヒト免疫学を中心に形態学的な側面からも，タイトジャンクションの詳細な変化を明らかにした点も学術的な意義があると思われる。さらに、本研究で明らかになったバリア機能の制御は、アレルギー性皮膚疾患だけでなく、ILCが関与する様々な疾患の病態を明らかにする手がかりとなる点で社会的意義があると考えられる。

Research Products

• [Journal Article] Outside-in hypothesis revisited (2020)
  • Author(s): Sugita Kazunari、Soyka Michael B.、Wawrzyniak Paulina、Rinaldi Arturo O.、Mitamura Yasutaka、Akdis M?beccel、Akdis Cezmi A.
  • Journal Title: Annals of Allergy, Asthma & Immunology Volume: 125 Issue: 5 Pages: 517-527
  • DOI: 10.1016/j.anai.2020.05.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recent developments and advances in atopic dermatitis and food allergy (2020)
  • Author(s): Sugita Kazunari、Akdis Cezmi A.
  • Journal Title: Allergology International Volume: 69 Issue: 2 Pages: 204-214
  • DOI: 10.1016/j.alit.2019.08.013
  • NAID: 130007832972
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Human type 2 innate lymphoid cells disrupt skin keratinocyte tight junction barrier by IL-13 (2019)
  • Author(s): Sugita K, Altunbulakli C, Morita H, Sugita A, Kubo T, Kimura R, Goto H, Yamamoto O, Rückert B, Akdis M, Akdis CA.
  • Journal Title: Allergy Volume: 74 Issue: 12 Pages: 2534-2537
  • DOI: 10.1111/all.13935
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Human type 2 innate lymphoid cells disrupt skin keratinocyte tight junction barrier by IL-13 (2019)
  • Author(s): Kazunari Sugita, Can Altunbulakli, Hideaki Morita, ,Terufumi Kubo, Beate Ruckert, Mubeccel Akdis, Cezmi A. Akdis
  • Organizer: 13th World Immune Regulation Meeting
  • Int'l Joint Research
• [Presentation] アレルギーと免疫治療 (2019)
  • Author(s): 杉田和成
  • Organizer: 第47回日本臨床免疫学会
  • Invited
• [Presentation] Type 2 innate lymphoid cells disrupt epithelial tight junction barrier by IL-13 (2019)
  • Author(s): Kazunari Sugita
  • Organizer: World Allergy Congress
  • Int'l Joint Research / Invited