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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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Related in: MedlinePlus

Expression of Th17 pathway molecules and serum Th17 associated cytokine level in LTS and CAD group.The expression of (A)IL-1beta(B)RAGE(C)HMGB1 mRNA was measured using real-time PCR. In addition, concentrations of (D) IL-17 (E) IL-33 and (F) RAGE were determined using ELISA in the serum of LTS and CAD patient group. Bars show the means. * P<0.05 vs. LTS. CAD, chronic allograft dysfunction; LTS, long term stable.
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pone.0145258.g006: Expression of Th17 pathway molecules and serum Th17 associated cytokine level in LTS and CAD group.The expression of (A)IL-1beta(B)RAGE(C)HMGB1 mRNA was measured using real-time PCR. In addition, concentrations of (D) IL-17 (E) IL-33 and (F) RAGE were determined using ELISA in the serum of LTS and CAD patient group. Bars show the means. * P<0.05 vs. LTS. CAD, chronic allograft dysfunction; LTS, long term stable.

Mentions: After PBMC were stimulated with PMA and ionomycin, the expression of mRNA for IL-1beta, RAGE, and HMGB1 was determined using real-time polymerase chain reaction. As shown in Fig 6A–6C, the expression of IL-1beta mRNA, RAGE mRNA and HMGB1 mRNA were suppressed in the LTS group compared to the CAD group (IL-1beta, P = 0.05; RAGE, P = 0.03; HMGB1, P = 0.07, vs. LTS). We also measured Th17 associated cytokine serum level isolated from same peripheral blood used for flowcytometric analysis and the results showed a similar trend (Fig 6D–6F); hence IL-17, IL-33, and RAGE levels showed a significant decrease in the LTS group compared to the CAD group (P<0.05 for all comparison).


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)

Expression of Th17 pathway molecules and serum Th17 associated cytokine level in LTS and CAD group.The expression of (A)IL-1beta(B)RAGE(C)HMGB1 mRNA was measured using real-time PCR. In addition, concentrations of (D) IL-17 (E) IL-33 and (F) RAGE were determined using ELISA in the serum of LTS and CAD patient group. Bars show the means. * P<0.05 vs. LTS. CAD, chronic allograft dysfunction; LTS, long term stable.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4696852&req=5

pone.0145258.g006: Expression of Th17 pathway molecules and serum Th17 associated cytokine level in LTS and CAD group.The expression of (A)IL-1beta(B)RAGE(C)HMGB1 mRNA was measured using real-time PCR. In addition, concentrations of (D) IL-17 (E) IL-33 and (F) RAGE were determined using ELISA in the serum of LTS and CAD patient group. Bars show the means. * P<0.05 vs. LTS. CAD, chronic allograft dysfunction; LTS, long term stable.
Mentions: After PBMC were stimulated with PMA and ionomycin, the expression of mRNA for IL-1beta, RAGE, and HMGB1 was determined using real-time polymerase chain reaction. As shown in Fig 6A–6C, the expression of IL-1beta mRNA, RAGE mRNA and HMGB1 mRNA were suppressed in the LTS group compared to the CAD group (IL-1beta, P = 0.05; RAGE, P = 0.03; HMGB1, P = 0.07, vs. LTS). We also measured Th17 associated cytokine serum level isolated from same peripheral blood used for flowcytometric analysis and the results showed a similar trend (Fig 6D–6F); hence IL-17, IL-33, and RAGE levels showed a significant decrease in the LTS group compared to the CAD group (P<0.05 for all comparison).

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