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Increase of Th17 Cell Phenotype in Kidney Transplant Recipients with Chronic Allograft Dysfunction.

Chung BH, Kim KW, Kim BM, Doh KC, Cho ML, Yang CW - PLoS ONE (2015)

Bottom Line: We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells.The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups.Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group.

View Article: PubMed Central - PubMed

Affiliation: Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul, Seoul, Korea.

ABSTRACT
This study was performed to determine the association of Th17 cell phenotype with chronic allograft dysfunction in kidney transplant recipients (KTRs). We compared the expression of Th17 cell phenotype in KTRs with chronic allograft dysfunction group (CAD, n = 52) with four control groups (long-term stable KTRs (LTS, n = 67), early stable KTRs (ES, n = 28), end stage renal disease (ESRD, n = 45), and healthy control (HC, n = 26). We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells. The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups. Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group. In vitro study revealed that IL-17 increased production of IL-6 and IL-8 and up-regulated profibrotic gene expression such as ACTA-2 and CTGF in HPRTEpiC in a dose-dependent manner, which suggests that IL-17 has a role in the development of renal tubular cell injury. The results of our study may suggest that increase of Th17 cell phenotype could be a marker for the chronic allograft injury; hence there is a need to develop diagnostic and therapeutic tools targeting the Th17 cells pathway.

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Distribution of allograft function in each study group.(A) Distribution of subjects according to allograft function and post-transplant years in LTS group and CAD group. Closed triangle mean the average value of MDRD eGFR at each post-transplant year in 587 patients who took kidney transplantation between 1995 and 2010 and current laboratory data is available in our center. (B) Comparison of allograft function assessed by MDRD eGFR in each study and control group. Note that allograft function was significantly superior in LTS group compared to CAD group. * P<0.05 for each comparison. LTS, long term stable; CAD, chronic allograft dysfunction; ES, early stable; ESRD, end stage renal disease; HC, healthy control; MDRD eGFR; Modification of Diet in Renal Disease estimated glomerular filtration rate.
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pone.0145258.g001: Distribution of allograft function in each study group.(A) Distribution of subjects according to allograft function and post-transplant years in LTS group and CAD group. Closed triangle mean the average value of MDRD eGFR at each post-transplant year in 587 patients who took kidney transplantation between 1995 and 2010 and current laboratory data is available in our center. (B) Comparison of allograft function assessed by MDRD eGFR in each study and control group. Note that allograft function was significantly superior in LTS group compared to CAD group. * P<0.05 for each comparison. LTS, long term stable; CAD, chronic allograft dysfunction; ES, early stable; ESRD, end stage renal disease; HC, healthy control; MDRD eGFR; Modification of Diet in Renal Disease estimated glomerular filtration rate.

Mentions: Before defining each group, we investigated the yearly change in the average value of estimated glomerular filtration rate (eGFR) calculated by Modification of Diet in Renal Disease (MDRD) equation in 587 patients who underwent kidney transplantation between 1995 and 2010 and the current laboratory data is available at our center (Fig 1A). Based on the results, the definition of the long-term stable group (LTS group) was patients who were at least 10 years post-transplantation and showed higher MDRD eGFR than the mean value at each concordant post-transplant year. The definition of the chronic allograft dysfunction (CAD) group was KTRs who were at least 2 years post-transplantation and showed MDRD eGFR less than 40 mL/min/1.73m2 and histological evidence of IF/TA (TA [ct≥1] and IF [ci≥1] involving more than 25% of the cortical area) [21]. Another three control groups were included; KTRs with a follow-up duration of less than 6 months after KT and showed stable clinical course were included in the early stable (ES) control group; End-stage renal disease (ESRD) patients who were on hemodialysis or peritoneal dialysis for at least 3 months were included in the ESRD group, and healthy volunteers who showed normal renal function without underlying renal disease were included in the healthy control (HC) group. Table 1 shows the baseline clinical characteristics of included patient population and Fig 1B shows the distribution of MDRD eGFR in each group. This study was approved by the Institutional Review Board (KC10SISI0235) of the Seoul St. Mary’s Hospital, and written informed consent was obtained from all patients.


Increase of Th17 Cell Phenotype in Kidney Transplant Recipients with Chronic Allograft Dysfunction.

Chung BH, Kim KW, Kim BM, Doh KC, Cho ML, Yang CW - PLoS ONE (2015)

Distribution of allograft function in each study group.(A) Distribution of subjects according to allograft function and post-transplant years in LTS group and CAD group. Closed triangle mean the average value of MDRD eGFR at each post-transplant year in 587 patients who took kidney transplantation between 1995 and 2010 and current laboratory data is available in our center. (B) Comparison of allograft function assessed by MDRD eGFR in each study and control group. Note that allograft function was significantly superior in LTS group compared to CAD group. * P<0.05 for each comparison. LTS, long term stable; CAD, chronic allograft dysfunction; ES, early stable; ESRD, end stage renal disease; HC, healthy control; MDRD eGFR; Modification of Diet in Renal Disease estimated glomerular filtration rate.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4696852&req=5

pone.0145258.g001: Distribution of allograft function in each study group.(A) Distribution of subjects according to allograft function and post-transplant years in LTS group and CAD group. Closed triangle mean the average value of MDRD eGFR at each post-transplant year in 587 patients who took kidney transplantation between 1995 and 2010 and current laboratory data is available in our center. (B) Comparison of allograft function assessed by MDRD eGFR in each study and control group. Note that allograft function was significantly superior in LTS group compared to CAD group. * P<0.05 for each comparison. LTS, long term stable; CAD, chronic allograft dysfunction; ES, early stable; ESRD, end stage renal disease; HC, healthy control; MDRD eGFR; Modification of Diet in Renal Disease estimated glomerular filtration rate.
Mentions: Before defining each group, we investigated the yearly change in the average value of estimated glomerular filtration rate (eGFR) calculated by Modification of Diet in Renal Disease (MDRD) equation in 587 patients who underwent kidney transplantation between 1995 and 2010 and the current laboratory data is available at our center (Fig 1A). Based on the results, the definition of the long-term stable group (LTS group) was patients who were at least 10 years post-transplantation and showed higher MDRD eGFR than the mean value at each concordant post-transplant year. The definition of the chronic allograft dysfunction (CAD) group was KTRs who were at least 2 years post-transplantation and showed MDRD eGFR less than 40 mL/min/1.73m2 and histological evidence of IF/TA (TA [ct≥1] and IF [ci≥1] involving more than 25% of the cortical area) [21]. Another three control groups were included; KTRs with a follow-up duration of less than 6 months after KT and showed stable clinical course were included in the early stable (ES) control group; End-stage renal disease (ESRD) patients who were on hemodialysis or peritoneal dialysis for at least 3 months were included in the ESRD group, and healthy volunteers who showed normal renal function without underlying renal disease were included in the healthy control (HC) group. Table 1 shows the baseline clinical characteristics of included patient population and Fig 1B shows the distribution of MDRD eGFR in each group. This study was approved by the Institutional Review Board (KC10SISI0235) of the Seoul St. Mary’s Hospital, and written informed consent was obtained from all patients.

Bottom Line: We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells.The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups.Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group.

View Article: PubMed Central - PubMed

Affiliation: Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul, Seoul, Korea.

ABSTRACT
This study was performed to determine the association of Th17 cell phenotype with chronic allograft dysfunction in kidney transplant recipients (KTRs). We compared the expression of Th17 cell phenotype in KTRs with chronic allograft dysfunction group (CAD, n = 52) with four control groups (long-term stable KTRs (LTS, n = 67), early stable KTRs (ES, n = 28), end stage renal disease (ESRD, n = 45), and healthy control (HC, n = 26). We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells. The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups. Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group. In vitro study revealed that IL-17 increased production of IL-6 and IL-8 and up-regulated profibrotic gene expression such as ACTA-2 and CTGF in HPRTEpiC in a dose-dependent manner, which suggests that IL-17 has a role in the development of renal tubular cell injury. The results of our study may suggest that increase of Th17 cell phenotype could be a marker for the chronic allograft injury; hence there is a need to develop diagnostic and therapeutic tools targeting the Th17 cells pathway.

Show MeSH
Related in: MedlinePlus