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- Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway.
Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway.
Citation | “Tissue-Resident Memory T Cells Mediate Immune Homeostasis In The Human Pancreas Through The Pd-1/Pd-L1 Pathway.”. Cell Reports, pp. 3916-3932.e5. . |
Center | Columbia University |
Author | Stuart P Weisberg, Dustin J Carpenter, Michael Chait, Pranay Dogra, Robyn D Gartrell-Corrado, Andrew X Chen, Sean Campbell, Wei Liu, Pooja Saraf, Mark E Snyder, Masaru Kubota, Nichole M Danzl, Beth A Schrope, Raul Rabadan, Yvonne Saenger, Xiaojuan Chen, Donna L Farber |
Keywords | PD-1, chronic pancreatitis, Macrophage, memory T cells, mucosal immunity, pancreas, tissue immunity |
Abstract |
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 CD8PD-1 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-macrophage interactions in controlling tissue homeostasis and immune dysfunctions underlying inflammatory disease, with important implications for PD-1-based immunotherapies. |
Year of Publication |
2019
|
Journal |
Cell reports
|
Volume |
29
|
Issue |
12
|
Number of Pages |
3916-3932.e5
|
Date Published |
12/2019
|
ISSN Number |
2211-1247
|
DOI |
10.1016/j.celrep.2019.11.056
|
Alternate Journal |
Cell Rep
|
PMID |
31851923
|
PMCID |
PMC6939378
|
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