“調控性T細胞”(Treg) 構成有效抗腫瘤免疫的一道屏障,。它們的刪除能誘導很多腫瘤的減小和清除,，但由于這些細胞在免疫系統(tǒng)中發(fā)揮重要的平衡作用，所以其刪除也會導致失控的自體免疫和死亡,。這篇論文描述了semaphorin-4a（T-細胞介導的免疫的一個活化劑）和neuropilin受體Nrp1在Treg細胞上的一種相互作用,，該相互作用是Treg細胞限制抗腫瘤免疫反應和治療已發(fā)生的炎性結腸炎所必需的，但對自體免疫的抑制和免疫自穩(wěn)的維持來說卻是可有可無的,。至于是否可以通過以Treg細胞為目標來限制腫瘤生長而又不會引發(fā)自體免疫,，其可行性仍有待確定。兩種生物活性也許是不可分開的,，但這項工作指出了可以對這一重要系統(tǒng)進一步定性的方向,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
Nature doi:10.1038/nature12428
Stability and function of regulatory T cells is maintained by a neuropilin-1–semaphorin-4a axis
Greg M. Delgoffe, Seng-Ryong Woo, Meghan E. Turnis, David M. Gravano, Cliff Guy, Abigail E. Overacre, Matthew L. Bettini, Peter Vogel, David Finkelstein, Jody Bonnevier, Creg J. Workman & Dario A. A. Vignali
Regulatory T cells (Treg cells) have a crucial role in the immune system by preventing autoimmunity, limiting immunopathology, and maintaining immune homeostasis1. However, they also represent a major barrier to effective anti-tumour immunity and sterilizing immunity to chronic viral infections1. The transcription factor Foxp3 has a major role in the development and programming of Treg cells2, 3. The relative stability of Treg cells at inflammatory disease sites has been a highly contentious subject4, 5, 6. There is considerable interest in identifying pathways that control the stability of Treg cells as many immune-mediated diseases are characterized by either exacerbated or limited Treg-cell function. Here we show that the immune-cell-expressed ligand semaphorin-4a (Sema4a) and the Treg-cell-expressed receptor neuropilin-1 (Nrp1) interact both in vitro, to potentiate Treg-cell function and survival, and in vivo, at inflammatory sites. Using mice with a Treg-cell-restricted deletion of Nrp1, we show that Nrp1 is dispensable for suppression of autoimmunity and maintenance of immune homeostasis, but is required by Treg cells to limit anti-tumour immune responses and to cure established inflammatory colitis. Sema4a ligation of Nrp1 restrained Akt phosphorylation cellularly and at the immunologic synapse by phosphatase and tensin homologue (PTEN), which increased nuclear localization of the transcription factor Foxo3a. The Nrp1-induced transcriptome promoted Treg-cell stability by enhancing quiescence and survival factors while inhibiting programs that promote differentiation. Importantly, this Nrp1-dependent molecular program is evident in intra-tumoral Treg cells. Our data support a model in which Treg-cell stability can be subverted in certain inflammatory sites, but is maintained by a Sema4a–Nrp1 axis, highlighting this pathway as a potential therapeutic target that could limit Treg-cell-mediated tumour-induced tolerance without inducing autoimmunity.
