|
Paper Reading Regulatory T Cells Promote Macrophage Efferocytosis during Inflammation Resolution Jonathan D. Proto, Amanda C. Doran et al Immunity, 2018 Regulatory T (Treg) cell responses and apoptotic cell clearance (efferocytosis) represent critical arms of the inflammation resolution response. Jonathan D. Proto and his colleagues sought to determine whether these processes might be linked through Treg-cell-mediated enhancement of efferocytosis. In this paper, the author found that Treg Cell depletion reduces the efferocytic capacity of peritoneal macrophages during resolution of inflammation while the depletion during the resolution phase after lipopolysaccharide-induced acute lung injury reduces efferocytosis by airspace macrophages. In advanced atherosclerosis, where defective efferocytosis drives disease progression, Treg cell expansion improved efferocytosis. The mechanistic studies revealed the following sequence: (1) Treg cells secreted interleukin-13 (IL-13), which stimulated IL-10 production in macrophages; (2) autocrine-paracrine signaling by IL-10 induced Vav1 in macrophages; and (3) Vav1 activated Rac1 to promote apoptotic cell engulfment. In summary, Treg cells promote macrophage efferocytosis during inflammation resolution via a transcellular signaling pathway that enhances apoptotic cell internalization. These findings suggest an expanded role of Treg cells in inflammation resolution and provide a mechanistic basis for Treg-cell-enhancement strategies for non-resolving inflammatory diseases.  Interleukin-17 Producing gd T Cells Originate from SOX13+ Progenitors that Are Independent of gdTCR Signaling Nicholas A. Spidale, Katelyn Sylvia, Kavitha Narayan et al. Immunity, 2018 Lineage-committed ab and gd T cells are thought to originate from common intrathymic multipotent progenitors following instructive T cell receptor (TCR) signals. A subset of lymph node and mucosal Vg2+ gd T cells is programmed intrathymically to produce IL-17 (Tgd17 cells), however the role of the gdTCR in development of these cells remains controversial. Here Nicholas A. Spidale and his group generated reporter mice for the Tgd17 lineage-defining transcription factor SOX13 and identified fetal-origin, intrathymic Sox13+ progenitors. In organ culture developmental assays, Tgd17 cells derived primarily from Sox13+ progenitors, and not from other known lymphoid progenitors. Single cell transcriptome assays of the progenitors found in TCR-deficient mice demonstrated that Tgd17 lineage programming was independent of gdTCR. Instead, generation of the lineage committed progenitors and Tgd17 cells was controlled by TCF1 and SOX13. Thus, T lymphocyte lineage fate can be prewired cell-intrinsically and is not necessarily specified by clonal antigen receptor signals.  Edited by Feng Xie  点击文首蓝字，关注我们 每一段文字都想与你分享 |
|
|
