| Autor: |
Nichole M. Danzl, Dustin J. Carpenter, Beth Schrope, Andrew X. Chen, Yvonne M. Saenger, Michael Chait, Robyn D. Gartrell-Corrado, Wei Liu, Stuart P. Weisberg, Pranay Dogra, Pooja Saraf, Donna L. Farber, Xiaojuan Chen, Sean R. Campbell, Mark E. Snyder, Masaru Kubota, Raul Rabadan |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| DOI: |
10.2139/ssrn.3445675 |
| Popis: |
Non-recirculating tissue resident memory T-cells (TRM) 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 TRM, which are phenotypically, functionally and transcriptionally distinct compared to TRM in neighboring jejunum and lymph node sites. Pancreas TRM 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, TRM 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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