Jialin Gao1, Zhonghua Jiang2, Shuai Wang1, Yuan Zhou1, Xiaolei Shi1, Min Feng1. 1. Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. 2. Department of Gastroenterology, The First People's Hospital of Yancheng, Yancheng, China.
Abstract
BACKGROUND AND AIM: Our previous studies have shown that regulatory T cells (Tregs) are reduced and Th17 cells are elevated in liver insults. Recent studies have indicated the critical role of endoplasmic reticulum (ER) stress of Kupffer cells (KCs) in evoking liver inflammation following reperfusion. The objective of this study was to investigate the role of ER stress of KCs in the conversion of Tregs to Th17 cells and the effect on liver ischemia-reperfusion injury. METHODS: The partial warm liver ischemia-reperfusion injury mouse model was adopted. ER stress of KCs and the frequency of Tregs and Th17 cells following reperfusion were analyzed. Apart from depletion and adoptive transfer of KCs, KCs were isolated from ischemic lobes and co-cultured with Tregs to study the effect of KCs on Tregs and Th17 cells. RESULTS: It was found that KCs induced ER stress, decreased natural Tregs (nTregs), and increased Th17 cells after reperfusion. Depletion of KCs modulated the reduction of nTregs and elevation of Th17 cells. Co-culture with stressed KCs led to the reduction in nTregs and elevation of Th17 cells. This effect was suppressed by anti-interleukin-6. Adoptive transfer of these stressed KCs resulted in the reduction in nTregs and elevation of Th17 cells and caused liver injury. CONCLUSION: Endoplasmic reticulum stress of KCs contributed to the conversion of nTregs to Th17 cells due to interleukin-6, resulting in the worsening of liver insult.
BACKGROUND AND AIM: Our previous studies have shown that regulatory T cells (Tregs) are reduced and Th17 cells are elevated in liver insults. Recent studies have indicated the critical role of endoplasmic reticulum (ER) stress of Kupffer cells (KCs) in evoking liver inflammation following reperfusion. The objective of this study was to investigate the role of ER stress of KCs in the conversion of Tregs to Th17 cells and the effect on liver ischemia-reperfusion injury. METHODS: The partial warm liver ischemia-reperfusion injurymouse model was adopted. ER stress of KCs and the frequency of Tregs and Th17 cells following reperfusion were analyzed. Apart from depletion and adoptive transfer of KCs, KCs were isolated from ischemic lobes and co-cultured with Tregs to study the effect of KCs on Tregs and Th17 cells. RESULTS: It was found that KCs induced ER stress, decreased natural Tregs (nTregs), and increased Th17 cells after reperfusion. Depletion of KCs modulated the reduction of nTregs and elevation of Th17 cells. Co-culture with stressed KCs led to the reduction in nTregs and elevation of Th17 cells. This effect was suppressed by anti-interleukin-6. Adoptive transfer of these stressed KCs resulted in the reduction in nTregs and elevation of Th17 cells and caused liver injury. CONCLUSION: Endoplasmic reticulum stress of KCs contributed to the conversion of nTregs to Th17 cells due to interleukin-6, resulting in the worsening of liver insult.
Authors: Young In Lee; Soo Min Kim; Jihee Kim; Jemin Kim; Seung Yong Song; Won Jai Lee; Ju Hee Lee Journal: Acta Derm Venereol Date: 2020-10-28 Impact factor: 3.875