期刊
CELL REPORTS
卷 29, 期 12, 页码 3916-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.11.056
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资金
- Bristol-Myers Squibb
- NIH [AI106697, K08 DK122130, T32 HL105323, T32GM007367, KL2TR001874]
- American Society of Transplantation TIRN award
- Parker B. Francis Foundation
- CRI Irvington Postdoctoral Fellowship
- Swim Across America
- NIH S10 shared instrumentation grants [1S10RR027050, S10OD020056, 5P30DK063608]
Non-recirculating tissue-resident memory T cells (TRMs) are the predominant T cell subset in diverse tissue sites, where they mediate protective immune responses in situ. Here, we reveal a role for TRM in maintaining immune homeostasis in the human pancreas through interactions with resident macrophages and the PD-1/PD-L1 inhibitory pathway. Using tissues obtained from organ donors, we identify that pancreas T cells comprise CD8(+)PD-1(hi) TRMs, which are phenotypically, functionally, and transcriptionally distinct compared to TRMs in neighboring jejunum and lymph node sites. Pancreas TRMs cluster with resident macrophages throughout the exocrine areas; TRM effector functions are enhanced by macrophage-derived co-stimulation and attenuated by the PD-1/PD-L1 pathways. Conversely, in samples from chronic pancreatitis, TRMs exhibit reduced PD-1 expression and reduced interactions with macrophages. These findings suggest important roles for PD-1 and TRM-macro-phage interactions in controlling tissue homeostasis and immune dysfunctions underlying inflammatory disease, with important implications for PD-1-based immunotherapies.
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