Limits...
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.

Show MeSH

Related in: MedlinePlus

Distribution of lymphocyte and CD4+ T cell in each patient group.PBMC from each patient group were stimulated for 4h ex vivo with PMA and ionomycin in the presence of Golgi Stop. The percentage of target cells was measured by flowcytometry. (A) The representative figure of flowcytometric analysis for lymphocyte and CD4+ T cell. (B) The proportion (%) of Lymphocyte/Total cells and (C) CD4+ T/Lymphocyte cells in each 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.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4696852&req=5

pone.0145258.g002: Distribution of lymphocyte and CD4+ T cell in each patient group.PBMC from each patient group were stimulated for 4h ex vivo with PMA and ionomycin in the presence of Golgi Stop. The percentage of target cells was measured by flowcytometry. (A) The representative figure of flowcytometric analysis for lymphocyte and CD4+ T cell. (B) The proportion (%) of Lymphocyte/Total cells and (C) CD4+ T/Lymphocyte cells in each 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: As shown in Fig 2, the percentage of lymphocytes and CD4+ T cells in the peripheral blood did not show differences in all groups. The proportions of Th1 (CD4+ IFN-γ+), Th2 (CD4+IL-4+), Th17 (CD4+IL-17+), and Treg (CD4+FOXP3+) out of CD4+ T cells are presented in Fig 3. The percentage of Th17 cells out of CD4+ T cells was significantly higher in the CAD group than in all other groups (P<0.001 for all, Fig 3B). In contrast, the proportion of Th1 cells did not show an increase in the CAD group compared to the other groups (Fig 3C). The proportion of Th2 cells did not differ between the LTS and CAD groups. But it was significantly higher in the ESRD group than in all other groups (P<0.001 respectively, Fig 3D). The proportion of Treg cells did not differ between the LTS and CAD groups (P = 0.67), meanwhile, all three transplant groups (LTS, CAD, and ES) showed a lower proportion of Treg cells compared to the ESRD group or the HC group (P<0.05 for each comparison, Fig 3E).


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 lymphocyte and CD4+ T cell in each patient group.PBMC from each patient group were stimulated for 4h ex vivo with PMA and ionomycin in the presence of Golgi Stop. The percentage of target cells was measured by flowcytometry. (A) The representative figure of flowcytometric analysis for lymphocyte and CD4+ T cell. (B) The proportion (%) of Lymphocyte/Total cells and (C) CD4+ T/Lymphocyte cells in each 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.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0145258.g002: Distribution of lymphocyte and CD4+ T cell in each patient group.PBMC from each patient group were stimulated for 4h ex vivo with PMA and ionomycin in the presence of Golgi Stop. The percentage of target cells was measured by flowcytometry. (A) The representative figure of flowcytometric analysis for lymphocyte and CD4+ T cell. (B) The proportion (%) of Lymphocyte/Total cells and (C) CD4+ T/Lymphocyte cells in each 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: As shown in Fig 2, the percentage of lymphocytes and CD4+ T cells in the peripheral blood did not show differences in all groups. The proportions of Th1 (CD4+ IFN-γ+), Th2 (CD4+IL-4+), Th17 (CD4+IL-17+), and Treg (CD4+FOXP3+) out of CD4+ T cells are presented in Fig 3. The percentage of Th17 cells out of CD4+ T cells was significantly higher in the CAD group than in all other groups (P<0.001 for all, Fig 3B). In contrast, the proportion of Th1 cells did not show an increase in the CAD group compared to the other groups (Fig 3C). The proportion of Th2 cells did not differ between the LTS and CAD groups. But it was significantly higher in the ESRD group than in all other groups (P<0.001 respectively, Fig 3D). The proportion of Treg cells did not differ between the LTS and CAD groups (P = 0.67), meanwhile, all three transplant groups (LTS, CAD, and ES) showed a lower proportion of Treg cells compared to the ESRD group or the HC group (P<0.05 for each comparison, Fig 3E).

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