Alternatively Activated Macrophages Boost Induced Regulatory T and Th17 Cell Responses during Immunotherapy for Colitis.
Alternatively Activated Macrophages Boost Induced Regulatory T and Th17 Cell Responses during Immunotherapy for Colitis.
复制标题
DOI：
10.4049/jimmunol.1501956
复制
发表时间：
2016-04-15
期刊：
影响因子：
--
通讯作者：
Williams CB
中科院分区：
文献类型：
--
作者：
Haribhai D;Ziegelbauer J;Jia S;Upchurch K;Yan K;Schmitt EG;Salzman NH;Simpson P;Hessner MJ;Chatila TA;Williams CB
Induced regulatory T (iTreg) and T helper 17 (Th17) cells promote mucosal homeostasis. We used a T cell transfer model of colitis to compare the capacity of iTreg and Th17 cells to develop in situ following the transfer of naïve CD4+ CD45RBhi T cells into Rag1−/− C57BL/6 or BALB/c mice, the prototypical Th1/M1- and Th2/M2-prone strains. We found that the frequency and number of Foxp3+ iTreg cells and Th17 cells were significantly reduced in C57BL/6 mice compared to the BALB/c strain. C57BL/6 mice with colitis were also resistant to nTreg cell immunotherapy. Pre-treatment of C57BL/6 Rag1−/− mice with IL-4 plus IL-13, or with M2a but not M1 macrophages, dramatically increased the generation of iTreg and Th17 cells. Importantly M2a transfers, either as a pretreatment or in mice with established colitis, allowed successful immunotherapy with nTreg cells. M2a macrophages also reduced the generation of pathogenic ex-iTreg cells, suggesting that they stabilize the expression of Foxp3. Thus polarized M2a macrophages drive a directionally concordant expansion of the iTreg -Th17 cell axis and can be exploited as a therapeutic adjuvant in cell-transfer immunotherapy to reestablish mucosal tolerance.
