2019-01-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/686009摘要：過去我們的研究已經發現，B 細胞具有誘發調節性T 細胞的能力。在此一計畫中，我們將進一步研究這群調節性T 細胞。我們在最初研究結果中除了證明由黏膜組織分離出來B 細胞，與樹突細胞和巨噬細胞相較之下會誘發出具有調節能力的Treg 細胞。我們之前的研究已經發現這群由B 細胞誘發的調節性T 細胞細胞會表現LAG-3 和PD-1 等分子，而且不需要Foxp-3 的表現就可以進行其免疫調節的能力。這些研究結果顯示我們研究團隊找到的這群Treg-of-B 細胞，與之前已經被找到的nTreg 和Tr1 細胞不盡相同，它們應該是一群新的調節性T 細胞。我們在過去幾年間也已經將這群Treg-of-B 細胞應用到各種免疫疾病，如氣喘、類風濕關節炎和發炎性腸道疾病，而且都得到相當不錯的治療效果。在我們接下來的研究計畫中將進一步研究這些Treg-of-B 細胞的特性，尤其是針對這群Treg-of-B 細胞的訊息傳導、可能的transcription factors 和細胞激素來進行研究。我們將分別利用microarray, real-time PCR 和transcriptome analysis with next generation sequencing 來尋找新的分子和基因，尤其是著重於STATs 的相關訊息和分子。由於STATs 相關的訊息在T 細胞的發育和功能上扮演了一個相當重要的角色，所以在此一計畫中我們也將進一步研究STATs 訊息傳導途徑在Treg-of-B 細胞發育和功能上所扮演的角色。此外，過去研究發現不同的STAT 蛋白參與不同T 細胞的生成，我們的初步研究成果也發現STAT6 參與Tregof-B(P)細胞的調控。因此，我們將進一步研究STAT6，和相關的分子與Treg-of-B 細胞生成之間的關係。我們相信這群新的調節性T 細胞如果能夠研究地更清楚，將有助於未來進一步將這些細胞應用到臨床免疫疾病的治療上。<br> Abstract: In this project, we aim to characterize and analyze regulatory T cells induced by B cells. In the past three years, our team has focused on exploring the haracteristics of a certain subpopulation of regulatory Tcells induced by B cells. This study aimed to icdentify the most critical molecules or genes involved in the functions of Treg-of-B cell. We have isolated and identified this particular subset of regulatory T cells. We have applied these Treg-of-B cells for the treatment of allergic airway inflammation with success. In addition, we have initially found that LAG3 molecule might play the critical role in the functions of Tregof-B cells. Further, the results also demonstrated that Foxp3 and IL-10 were not necessary for the development and functions of Treg-of-B cells. All these results suggested that these Treg-of-B cells are different from the conventional naturally occurring regulatory T cells (nTreg cells) and inducible type 1 regulatory T cells (Tr1 cells). The regulatory T cells described in our proposal could be the novel subset of the regulatory T cells, which might open the brand new approaches for the pathway of immune regulation. Since our team has demonstrated that the Treg-of-B cells induced by Peyer’s patch B cells could exert the therapeutic effect, suggesting that Treg-of-B cells might contribute to mucosal tolerance. Previous studies mentioned that the activation of STATs plays the critical role in different T cell subset generation. Our study also showed that STAT6 phosphorylation could induce Treg-of-B(P) cells. In this project, we like to clarify the detail of the interaction of STATs and related molecules in the Treg-of-B(P) cell induction. From microarray result, we also found that CD200 might participate in Treg-of-B(P) cellgeneration. We believe that the more detail discovering, we could apply this cell population on treating inflammatory diseases more efficiently.黏膜耐受性調節性T 細胞mucosal toleranceTreg cell