Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway
| Autor: | Robyn D. Gartrell-Corrado, Andrew X. Chen, Sean R. Campbell, Yvonne M. Saenger, Nichole M. Danzl, Donna L. Farber, Pooja Saraf, Mark E. Snyder, Pranay Dogra, Wei Liu, Stuart P. Weisberg, Dustin J. Carpenter, Raul Rabadan, Michael Chait, Masaru Kubota, Xiaojuan Chen, Beth Schrope |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed Cell Death 1 Receptor Biology B7-H1 Antigen Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immune system T-Lymphocyte Subsets PD-L1 medicine Humans Macrophage Immunity Mucosal Pancreas lcsh:QH301-705.5 Lymph node Tissue homeostasis Macrophages CD58 Antigens medicine.disease 3. Good health Cell biology 030104 developmental biology medicine.anatomical_structure Pancreatitis lcsh:Biology (General) biology.protein Immunologic Memory 030217 neurology & neurosurgery CD8 Signal Transduction |
| Zdroj: | Cell Reports, Vol 29, Iss 12, Pp 3916-3932.e5 (2019) Cell reports |
| ISSN: | 2211-1247 |
| 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 bay 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. Graphical Abstract In Brief 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. |
| Databáze: | OpenAIRE |
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