| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 29, Iss 12, Pp 3916-3932.e5 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.11.056 |
| Popis: |
Summary: 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-1hi 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. : Non-recirculating tissue-resident memory T cells (TRMs) mediate immune responses in non-lymphoid tissues. Using a human organ donor tissue resource, Weisberg et al. reveal that PD-1hi pancreas TRMs are regulated by PD-L1+ macrophages during homeostasis. Comparison with chronic pancreatitis patient samples shows how pancreas TRM regulation is altered during inflammation. Keywords: memory T cells, pancreas, chronic pancreatitis, tissue immunity, mucosal immunity, PD-1, macrophage |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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