Tissue-resident regulatory T cells exert dualistic anti-tumour and pro-repair function in the exocrine pancreas
Regulatory T cells are fundamentally important for maintaining immune homeostasis, and their potent immune-suppressive roles make them attractive immunotherapeutic targets in cancer. Recent work suggests potential functions of tissue-resident Tregs (trTregs) in tissue-repair and epithelial cell homeostasis. Here, we describe a rare population of trTreg in the exocrine pancreas. We show that these cells share common features of trTregs, including expression of the IL-33 receptor ST2 and production of the epithelial growth factor Amphiregulin, and display an oligoclonal T cell receptor repertoire. Using a mouse model of acute pancreatitis, we show that pancreatic Tregs rapidly expand upon release of IL-33 by fibroblasts. Moreover, depletion of Tregs after initiation of pancreatic injury impairs the regeneration of the exocrine parenchyma. This effect is due, in part, through a direct effect of Tregs on acinar cell proliferation. Finally, we show that transient Treg depletion in established orthotopic pancreatic tumours leads to tumour rejection yet provokes long-lasting damages to surrounding exocrine parenchyma. In all, our results demonstrate the tissue-repair capacity of pancreatic Tregs, and highlight a dualistic role of these cells in the pancreatic tumour ecosystem, with their harmful immune-suppressive function in the tumour coupled to a beneficial tissue-repair function in the surrounding tissue..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 19. Feb. Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Stockis, Julie [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2024.02.15.580302 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI042560500 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI042560500 | ||
| 003 | DE-627 | ||
| 005 | 20240220090610.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240220s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2024.02.15.580302 |2 doi | |
| 035 | |a (DE-627)XBI042560500 | ||
| 035 | |a (biorXiv)10.1101/2024.02.15.580302 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Stockis, Julie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tissue-resident regulatory T cells exert dualistic anti-tumour and pro-repair function in the exocrine pancreas |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Regulatory T cells are fundamentally important for maintaining immune homeostasis, and their potent immune-suppressive roles make them attractive immunotherapeutic targets in cancer. Recent work suggests potential functions of tissue-resident Tregs (trTregs) in tissue-repair and epithelial cell homeostasis. Here, we describe a rare population of trTreg in the exocrine pancreas. We show that these cells share common features of trTregs, including expression of the IL-33 receptor ST2 and production of the epithelial growth factor Amphiregulin, and display an oligoclonal T cell receptor repertoire. Using a mouse model of acute pancreatitis, we show that pancreatic Tregs rapidly expand upon release of IL-33 by fibroblasts. Moreover, depletion of Tregs after initiation of pancreatic injury impairs the regeneration of the exocrine parenchyma. This effect is due, in part, through a direct effect of Tregs on acinar cell proliferation. Finally, we show that transient Treg depletion in established orthotopic pancreatic tumours leads to tumour rejection yet provokes long-lasting damages to surrounding exocrine parenchyma. In all, our results demonstrate the tissue-repair capacity of pancreatic Tregs, and highlight a dualistic role of these cells in the pancreatic tumour ecosystem, with their harmful immune-suppressive function in the tumour coupled to a beneficial tissue-repair function in the surrounding tissue. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Yip, Thomas |4 aut | |
| 700 | 1 | |a Raghunathan, Shwetha |4 aut | |
| 700 | 1 | |a Garcia, Celine |4 aut | |
| 700 | 1 | |a Lee, Sheng |4 aut | |
| 700 | 1 | |a Simpson, Charlotte |4 aut | |
| 700 | 1 | |a Silvain, Silvain |4 aut | |
| 700 | 1 | |a Schuijs, Martijn J. |4 aut | |
| 700 | 1 | |a Araos, Joaquin |4 aut | |
| 700 | 1 | |a Png, Shaun |4 aut | |
| 700 | 1 | |a Raddi, Gianmarco |4 aut | |
| 700 | 1 | |a Bricard, Orian |4 aut | |
| 700 | 1 | |a So, Tsz Y. |4 aut | |
| 700 | 1 | |a Mack, Stephanie |4 aut | |
| 700 | 1 | |a Papadopoulos, Panagiotis |4 aut | |
| 700 | 1 | |a Sawle, Ashley |4 aut | |
| 700 | 1 | |a Jodrell, Duncan I. |4 aut | |
| 700 | 1 | |a McKenzie, Andrew N.J. |4 aut | |
| 700 | 1 | |a Thaventhiran, James |0 (orcid)0000-0001-8616-074X |4 aut | |
| 700 | 1 | |a Clatworthy, Menna |4 aut | |
| 700 | 1 | |a Biffi, Giulia |4 aut | |
| 700 | 1 | |a Saeb-Parsy, Kourosh |4 aut | |
| 700 | 1 | |a Liston, Adrian |4 aut | |
| 700 | 1 | |a Halim, Timotheus Y.F. |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2024) vom: 19. Feb. |
| 773 | 1 | 8 | |g year:2024 |g day:19 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2024.02.15.580302 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 19 |c 02 | ||