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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 Tnaïve, TCM, TEM subpopulations of CD4+T lymphocytes and IL-17+/TEM subpopulations of CD4+ T lymphocytes.(A) PBMCs were stained with anti-CD4 PE-cy7, anti-CD45RA–FITC, anti-CCR7 APC and anti-IL-17 PE. CD4+ T cells were gated for further analysis. (B) The proportion (%) of Tnaïve/CD4+ T (CD45RA+CCR7+/CD4+ Tcells) (C) TCM/CD4+ T (CD45RA–CCR7+/CD4+Tcells) (D) TEM/CD4+ T (CD45RA–CCR7–/CD4+ Tcells) (E) After surface staining with CD45 and CCR7 mAbs, analysis of IL-17 in CD4+ T cell subsets by intracellular flow cytometry was done. (F) The proportion (%) of IL-17+/TEM. in each patient 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.
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pone.0145258.g004: Distribution of Tnaïve, TCM, TEM subpopulations of CD4+T lymphocytes and IL-17+/TEM subpopulations of CD4+ T lymphocytes.(A) PBMCs were stained with anti-CD4 PE-cy7, anti-CD45RA–FITC, anti-CCR7 APC and anti-IL-17 PE. CD4+ T cells were gated for further analysis. (B) The proportion (%) of Tnaïve/CD4+ T (CD45RA+CCR7+/CD4+ Tcells) (C) TCM/CD4+ T (CD45RA–CCR7+/CD4+Tcells) (D) TEM/CD4+ T (CD45RA–CCR7–/CD4+ Tcells) (E) After surface staining with CD45 and CCR7 mAbs, analysis of IL-17 in CD4+ T cell subsets by intracellular flow cytometry was done. (F) The proportion (%) of IL-17+/TEM. in each patient 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.

Mentions: Staining of peripheral blood T cells with antibodies to CD45RA and CCR7 showed three subsets of CD4+ cells; one naïve CD45RA+CCR7+ subset (Tnaive) and two memory subsets, CD45RA–CCR7+ central memory T cells (TCM) and CD45RA–CCR7– effector memory T cells (TEM) (Fig 4A). No difference was detected in the percentage of Tnaive (P = 0.48), TCM (P = 0.37) and TEM (P = 0.64) between the LTS and CAD groups (Fig 4B–4D). However, the percentage of Tnaive showed a significant decrease in ESRD patients compared to other patient groups (P<0.001 for each comparison, Fig 4B). In contrast, TEM showed a significant increase in the ESRD group compared to other groups (P<0.001 for each comparison). The proportion of IL-17 producing cells was significantly higher in the CD4+ TEM subset in patients of the CAD group compared to patients of the LTS group (P<0.001, Fig 4E and 4F).


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 Tnaïve, TCM, TEM subpopulations of CD4+T lymphocytes and IL-17+/TEM subpopulations of CD4+ T lymphocytes.(A) PBMCs were stained with anti-CD4 PE-cy7, anti-CD45RA–FITC, anti-CCR7 APC and anti-IL-17 PE. CD4+ T cells were gated for further analysis. (B) The proportion (%) of Tnaïve/CD4+ T (CD45RA+CCR7+/CD4+ Tcells) (C) TCM/CD4+ T (CD45RA–CCR7+/CD4+Tcells) (D) TEM/CD4+ T (CD45RA–CCR7–/CD4+ Tcells) (E) After surface staining with CD45 and CCR7 mAbs, analysis of IL-17 in CD4+ T cell subsets by intracellular flow cytometry was done. (F) The proportion (%) of IL-17+/TEM. in each patient 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.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4696852&req=5

pone.0145258.g004: Distribution of Tnaïve, TCM, TEM subpopulations of CD4+T lymphocytes and IL-17+/TEM subpopulations of CD4+ T lymphocytes.(A) PBMCs were stained with anti-CD4 PE-cy7, anti-CD45RA–FITC, anti-CCR7 APC and anti-IL-17 PE. CD4+ T cells were gated for further analysis. (B) The proportion (%) of Tnaïve/CD4+ T (CD45RA+CCR7+/CD4+ Tcells) (C) TCM/CD4+ T (CD45RA–CCR7+/CD4+Tcells) (D) TEM/CD4+ T (CD45RA–CCR7–/CD4+ Tcells) (E) After surface staining with CD45 and CCR7 mAbs, analysis of IL-17 in CD4+ T cell subsets by intracellular flow cytometry was done. (F) The proportion (%) of IL-17+/TEM. in each patient 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.
Mentions: Staining of peripheral blood T cells with antibodies to CD45RA and CCR7 showed three subsets of CD4+ cells; one naïve CD45RA+CCR7+ subset (Tnaive) and two memory subsets, CD45RA–CCR7+ central memory T cells (TCM) and CD45RA–CCR7– effector memory T cells (TEM) (Fig 4A). No difference was detected in the percentage of Tnaive (P = 0.48), TCM (P = 0.37) and TEM (P = 0.64) between the LTS and CAD groups (Fig 4B–4D). However, the percentage of Tnaive showed a significant decrease in ESRD patients compared to other patient groups (P<0.001 for each comparison, Fig 4B). In contrast, TEM showed a significant increase in the ESRD group compared to other groups (P<0.001 for each comparison). The proportion of IL-17 producing cells was significantly higher in the CD4+ TEM subset in patients of the CAD group compared to patients of the LTS group (P<0.001, Fig 4E and 4F).

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