Monocytes as potential mediators of pathogen-induced Th17 differentiation in patients with primary sclerosing cholangitis (PSC)
Standard
Monocytes as potential mediators of pathogen-induced Th17 differentiation in patients with primary sclerosing cholangitis (PSC). / Kunzmann, Lilly Kristin; Schoknecht, Tanja; Poch, Tobias; Henze, Lara; Stein, Stephanie; Kriz, Marvin; Grewe, Ilka; Preti, Max; Hartl, Johannes; Pannicke, Nadine; Peiseler, Moritz; Sebode, Marcial; Zenouzi, Roman; Horvatits, Thomas; Böttcher, Marius; Petersen, Britt-Sabina; Weiler-Normann, Christina; Hess, Leonard U; Ahrenstorf, Annika Elise; Lunemann, Sebastian; Martrus, Gloria; Fischer, Lutz; Li, Jun; Carambia, Antonella; Kluwe, Johannes; Huber, Samuel; Lohse, Ansgar W; Franke, Andre; Herkel, Johannes; Schramm, Christoph; Schwinge, Dorothee.
In: HEPATOLOGY, Vol. 72, No. 4, 23.01.2020, p. 1310-1326.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Monocytes as potential mediators of pathogen-induced Th17 differentiation in patients with primary sclerosing cholangitis (PSC)
AU - Kunzmann, Lilly Kristin
AU - Schoknecht, Tanja
AU - Poch, Tobias
AU - Henze, Lara
AU - Stein, Stephanie
AU - Kriz, Marvin
AU - Grewe, Ilka
AU - Preti, Max
AU - Hartl, Johannes
AU - Pannicke, Nadine
AU - Peiseler, Moritz
AU - Sebode, Marcial
AU - Zenouzi, Roman
AU - Horvatits, Thomas
AU - Böttcher, Marius
AU - Petersen, Britt-Sabina
AU - Weiler-Normann, Christina
AU - Hess, Leonard U
AU - Ahrenstorf, Annika Elise
AU - Lunemann, Sebastian
AU - Martrus, Gloria
AU - Fischer, Lutz
AU - Li, Jun
AU - Carambia, Antonella
AU - Kluwe, Johannes
AU - Huber, Samuel
AU - Lohse, Ansgar W
AU - Franke, Andre
AU - Herkel, Johannes
AU - Schramm, Christoph
AU - Schwinge, Dorothee
N1 - © 2020 by the American Association for the Study of Liver Diseases.
PY - 2020/1/23
Y1 - 2020/1/23
N2 - T cells from patients with primary sclerosing cholangitis (PSC) show a prominent IL-17 response upon stimulation with bacteria or fungi, yet the reasons for this dominant TH17 response in PSC are not clear. Here, we analyzed the potential role of monocytes in microbial recognition and in skewing the T cell response towards Th17. Monocytes and T cells from blood and livers of PSC patients and controls were analyzed ex vivo and in vitro using trans-well experiments with cholangiocytes. Cytokine production was measured using flow cytometry, ELISA, RNA in situ hybridization and quantitative real time PCR. Genetic polymorphisms were obtained from Immunochip analysis. Following ex vivo stimulation with PMA/Ionomycin, PSC patients showed significantly increased numbers of IL-17A-producing peripheral blood CD4+ T cells compared to PBC patients and healthy controls, indicating increased Th17 differentiation in vivo. Upon stimulation with microbes, monocytes from PSC patients produced significantly more IL-1β and IL-6, cytokines known to drive Th17 cell differentiation. Moreover, microbe-activated monocytes induced the secretion of Th17 and monocyte-recruiting chemokines CCL-20 and CCL-2 in human primary cholangiocytes. In livers of patients with PSC cirrhosis, CD14hi CD16int and CD14lo CD16hi monocytes/macrophages were increased compared to alcoholic cirrhosis and monocytes were found to be located around bile ducts. Conclusion: PSC patients show increased Th17 differentiation already in vivo. Microbe-stimulated monocytes drive Th17 differentiation in vitro and induce cholangiocytes to produce chemokines mediating recruitment of Th17 cells and more monocytes into portal tracts. Taken together, these results point to a pathogenic role of monocytes in patients with PSC.
AB - T cells from patients with primary sclerosing cholangitis (PSC) show a prominent IL-17 response upon stimulation with bacteria or fungi, yet the reasons for this dominant TH17 response in PSC are not clear. Here, we analyzed the potential role of monocytes in microbial recognition and in skewing the T cell response towards Th17. Monocytes and T cells from blood and livers of PSC patients and controls were analyzed ex vivo and in vitro using trans-well experiments with cholangiocytes. Cytokine production was measured using flow cytometry, ELISA, RNA in situ hybridization and quantitative real time PCR. Genetic polymorphisms were obtained from Immunochip analysis. Following ex vivo stimulation with PMA/Ionomycin, PSC patients showed significantly increased numbers of IL-17A-producing peripheral blood CD4+ T cells compared to PBC patients and healthy controls, indicating increased Th17 differentiation in vivo. Upon stimulation with microbes, monocytes from PSC patients produced significantly more IL-1β and IL-6, cytokines known to drive Th17 cell differentiation. Moreover, microbe-activated monocytes induced the secretion of Th17 and monocyte-recruiting chemokines CCL-20 and CCL-2 in human primary cholangiocytes. In livers of patients with PSC cirrhosis, CD14hi CD16int and CD14lo CD16hi monocytes/macrophages were increased compared to alcoholic cirrhosis and monocytes were found to be located around bile ducts. Conclusion: PSC patients show increased Th17 differentiation already in vivo. Microbe-stimulated monocytes drive Th17 differentiation in vitro and induce cholangiocytes to produce chemokines mediating recruitment of Th17 cells and more monocytes into portal tracts. Taken together, these results point to a pathogenic role of monocytes in patients with PSC.
U2 - 10.1002/hep.31140
DO - 10.1002/hep.31140
M3 - SCORING: Journal article
C2 - 31975436
VL - 72
SP - 1310
EP - 1326
JO - HEPATOLOGY
JF - HEPATOLOGY
SN - 0270-9139
IS - 4
ER -