Study of functional characteristics of cytotoxic Tfh cells and their pathological significance
Project/Area Number |
18H02632
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 49020:Human pathology-related
|
Research Institution | Sapporo Medical University |
Principal Investigator |
|
Project Period (FY) |
2018-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
|
Keywords | 濾胞ヘルパーT細胞 / 記憶B細胞 / DP-Tfh細胞 / 細胞傷害性Tfh細胞 / IgG4関連疾患 / 異所性リンパ組織 / Eomes / CD70 / 慢性炎症 / 線維化 / ミクリッツ病 / 細胞傷害性DP-Tfh細胞 / 細胞傷害性CD4T細胞 / 3次リンパ組織 / CD8 / IL-7 / Tfh細胞 / 線維性炎症 / ヒト免疫システム / Bob1 / Tfr細胞 / クラススイッチ機構 / 扁桃 / 扁桃組織 / CTL活性 / 臨床検体 / 細胞傷害活性 / 免疫関連疾患 |
Outline of Final Research Achievements |
This study aimed to characterize the functional features of T follicular helper cells (Tfh cells) in ectopic lymphoid tissues with chronic inflammation. The analysis of fibroinflammatory lesions of IgG4-related disease (IgG4-RD) revealed that the Tfh cell population contained double-positive Tfh cells (DP-Tfh cells), which expressed both CD4 and CD8 and presented cytotoxicity-related molecules, including Eomes, granzymes, perforin, CRTAM, and GPR56. Studies of clinical parameters and co-culture experiments using autologous T and B cells suggest that DP-Tfh cells would regulate memory B cells. Further in vitro experiments showed that normal Tfh cells could differentiate into DP-Tfh cells under the stimulation with IL-2 and IL-7, which was highly expressed in the tissue lesions of IgG4-RD. Taken together, DP-Tfh cells may play a possible role in inhibiting memory B cell function to control the antibody production program within a persistent inflammatory environment.
|
Academic Significance and Societal Importance of the Research Achievements |
Tfh細胞はリンパ濾胞胚中心の形成を調節し、抗原特異的な抗体の産生と液性免疫記憶の成立に関わるヘルパーT細胞である。臨床検体を用いた本研究から、異所性リンパ濾胞の形成を伴う3次免疫リンパ組織において細胞傷害活性を有するDP-Tfh細胞が多く検出され、B細胞による免疫記憶を調節する新たなメカニズムが示された。本研究は慢性炎症病態のさらなる理解につながり、また重症ウイルス感染症では細胞傷害性Tfh細胞が高頻度に認められるため、免疫関連疾患の病態背景のみならず、感染防御機構の研究においても意義ある成果と考えられる。
|
Report
(5 results)
Research Products
(63 results)
-
-
[Journal Article] Cytotoxic Tph-like cells are involved in persistent tissue damage in IgG4-related disease.2020
Author(s)
Yabe H, Kamekura R, Yamamoto M, Murayama K, Kamiya S, Ikegami I, Shigehara K, Takaki H, Chiba H, Takahashi H, Takano K, Takahashi H, Ichimiya S.
-
Journal Title
Mod Rheumatol.
Volume: Feb 5
Issue: 1
Pages: 1-12
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Activated circulating T follicular helper cells and skewing of T follicular helper 2 cells are down-regulated by treatment including an inhaled corticosteroid in patients with allergic asthma2020
Author(s)
Miyajima S, Shigehara K, Kamekura R, Takaki H, Yabe H, Ikegami I, Asai Y, Nishikiori H, Chiba H, Uno E, Takahashi H, Ichimiya S.
-
Journal Title
Allergology International
Volume: 69
Issue: 1
Pages: 66-77
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
[Journal Article] IL-10+ T follicular regulatory cells are associated with the pathogenesis of IgG4-related disease.2019
Author(s)
Ito F, Kamekura R, Yamamoto M, Takano K, Takaki H, Yabe, H, Ikegami I, Shigehara K, Himi T, Takahashi H, Ichimiya S.
-
Journal Title
Immunol Lett.
Volume: 207
Pages: 56-63
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Predicting therapeutic response in IgG4-related disease based on cluster analysis.2018
Author(s)
Yamamoto M, Takano K, Kamekura R, Suzuki C, Tabeya T, Murakami R, Honda S, Mukai M, Nojima M, Ichimiya S, Himi T, Nakase H, Takahashi H.
-
Journal Title
Immunological Medicine.
Volume: 41
Issue: 1
Pages: 30-33
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] Circulating PD-1(+)CXCR5(-)CD4(+) T cells underlying the immunological mechanisms of IgG4-related disease.2018
Author(s)
Kamekura R, Yamamoto M, Takano K, Yabe H, Ito F, Ikegami I, Takaki H, Shigehara K, Suzuki C, Himi T, Takahashi H, Ichimiya S.
-
Journal Title
Rheumatology Advances in Practice
Volume: 2
Issue: 2
Pages: 1-7
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-