PMID- 32971208 OWN - NLM STAT- MEDLINE DCOM- 20220113 LR - 20220531 IS - 1878-5492 (Electronic) IS - 0966-3274 (Linking) VI - 65 DP - 2021 Apr TI - Mechanisms underlying the production of chemokine CXCL11 in the reaction of renal tubular epithelial cells with CD4(+) and CD8(+) T cells. PG - 101337 LID - S0966-3274(19)30148-0 [pii] LID - 10.1016/j.trim.2020.101337 [doi] AB - AIM: To study the release mechanism of C-X-C motif chemokine 11 (CXCL11) and other chemokines after the co-cultivation of CD4(+) and CD8(+) T cells with the renal tubular epithelial cells (RTEC) in the process of allograft renal transplantation rejection. METHODS: The Human CD4(+), CD8(+) T cells were obtained from the blood of volunteers and kidney transplantation (Ktx) patients, and co-cultured with renal tubular epithelial cells (RTEC) in vitro. RT-PCR was run for detecting the mRNA transcription of CXCL11, IFN-induced protein of 10 (CXCL10), and IL-6 in cells after RTEC was stimulated with IFN-gamma or co-cultured with CD4(+) and CD8(+) T cells. The concentration of CXCL11, CXCL10 and IL-6 in the culture medium was detected by Multiplex Assay after RTEC was stimulated with IFN-gamma or co-cultured with CD4(+) and CD8(+) T cells. IFN-gamma receptor antibody was used for interfering with the above reaction and the blocking effect was observed. Western blot was used for protein expression analysis. Finally, we applied renal biopsies from kidney transplantation patients with and without rejection to verify the results of the above experiments by using RT-PCR and Western blot. RESULTS: The mRNA expression of CXCL11 and CXCL10 were significantly increased after RTEC was stimulated with IFN-gamma or co-cultured with CD4(+) and CD8(+) T cells. Multiplex Assay showed that the concentration of CXCL11 and CXCL10 in the supernatant were significantly increased in a time-dependence fashion after stimulation RTEC by IFN-gamma. Anti-IFN-gamma receptor1 (anti-IFN-gammaR1) antibody could reduce the production of CXCL11 and CXCL10 in this situation. The concentration of CXCL11 and CXCL11 in the supernatant was significantly increased with a time-dependent effect after the co-culture of CD4(+) and CD8(+) T cells with RTEC. The anti-IFN-gammaR1 blocked this effect. Our study showed that the expression levels of CXCL11 and CXCL10 were upgraded in the biopsies of patients with renal transplant rejection comparatively to pre-transplant biopsies, both at mRNA and protein levels. CONCLUSIONS: RTEC and T cells can stimulate each other during the acute rejection of allogeneic kidney transplantation and secret CXCL11,CXCL10 and other chemokines. IFN-gamma plays a key role in this process. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Wang, Xiaoping AU - Wang X AD - Department of Nephrology, Shandong University & Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250000, China. Electronic address: wang13395413385@163.com. FAU - Wang, Dan AU - Wang D AD - Department of Nephrology, Shandong University & Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250000, China. Electronic address: wangdan198566@163.com. FAU - Wang, Xiao AU - Wang X AD - Department of Nephrology, Shandong University & Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250000, China. Electronic address: 1538253780@qq.com. FAU - Wang, Xiaoqi AU - Wang X AD - Department of Cardiology, Shandong University & Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250000, China. Electronic address: wangqiqi86@sina.com. FAU - Sha, Ji-Chang AU - Sha JC AD - Department of Neurosurgery, Zhangqiu District People's Hospital, Jinan 250200, China. Electronic address: wangqiqi86@sina.com. FAU - Gao, Qingzhen AU - Gao Q AD - Department of Nephrology, Shandong University & Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250000, China. Electronic address: qingzhengaogao@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200921 PL - Netherlands TA - Transpl Immunol JT - Transplant immunology JID - 9309923 RN - 0 (CXCL11 protein, human) RN - 0 (Chemokine CXCL10) RN - 0 (Chemokine CXCL11) RN - 0 (Chemokine CXCL9) SB - IM MH - CD4-Positive T-Lymphocytes MH - *CD8-Positive T-Lymphocytes MH - *Chemokine CXCL10 MH - Chemokine CXCL11 MH - Chemokine CXCL9 MH - Epithelial Cells MH - Humans OTO - NOTNLM OT - Allograft renal transplantation rejection OT - Chemokine OT - IFN-inducible T cell chemoattractant OT - Renal tubular epithelial cells EDAT- 2020/09/25 06:00 MHDA- 2022/01/14 06:00 CRDT- 2020/09/24 20:10 PHST- 2019/10/15 00:00 [received] PHST- 2020/09/15 00:00 [revised] PHST- 2020/09/19 00:00 [accepted] PHST- 2020/09/25 06:00 [pubmed] PHST- 2022/01/14 06:00 [medline] PHST- 2020/09/24 20:10 [entrez] AID - S0966-3274(19)30148-0 [pii] AID - 10.1016/j.trim.2020.101337 [doi] PST - ppublish SO - Transpl Immunol. 2021 Apr;65:101337. doi: 10.1016/j.trim.2020.101337. Epub 2020 Sep 21.