Increased IL-21 expression in primary biliary cirrhosis patients and its implications

Abstract

Objective To investigate the role of IL-21 in the pathogenesis of primary biliary cirrhosis (PBC). Methods Serum IL-21 and IL-17 level of 32 PBC patients and 26 healthy individuals who first vistited the Changzheng hospital between February 2010 and February 2011 were determined by ELISA.The percentage of Th17 and Treg were detected by flow cytometry and their associations with serum IL-21 were assessed by Spearman.Dendritic cells loading pyruvate dehydrogenase complex E2 subunit (PDC-E2) polypeptides were cocultured with initial T helper cells to induce PDC-E2 reactive Th17 and Treg cells in vitro.Flow cytometry was applied to determine the effect of IL-21 (at concentration of 20 ng/L) on the differentiation of PDC-E2 reactive T cells. Results The levels of IL-21 in PBC patients and healthy individuals were 569 (356-735) and 228 (134-345) ng/L respectively,the levels of IL-17 were 18.8 (13.1-25.5) and 7.3 (4.6-9.1) ng/L.Th17 cell percentages in peripheral blood were 3.24% (2.47%-3.97%) and 0.90% (0.48%-1.19%).Treg cell percentages were 3.68% (2.28%-4.53%) and 7.74% (6.23%-9.55%),the Z values of IL-21,IL-17,Th17 and Treg were 5.25,5.69,6.27 and 5.22,(P<0.01 for both).The level of serum IL-21 in PBC patients was positively correlated with IL-17 and Th17 cells percentage (correlation coefficient r was 0.54 and 0.47 respectively,P<0.01 for both),while negatively correlated with Treg cells percentage (correlation coefficient r was -0.62,P<0.01).In the co-culture system contain dendritic cells and naive Th cells,the percentage of Th17 cells and Treg cells after adding IL-21 were (83.8±4.3)% and (3.8±0.70)%,respectively. By contrast, Th17 and Treg percentage in IL-21 treated co-culture system were (72.0±6.8)% and (6.2±0.4)%,respectively.The different had statistical significance (Z value were 2.40 and 2.62, P<0.01 for both). Conclusion IL-21 is involved in the pathogenesis of PBC via regulating PDC-E2 reactive Th17/Treg cell balance,and could be regarded as a potential therapy target.(Chin J Lab Med,2013,36:222-227) Key words: Liver cirrhosis; primary; Interleukins; T-lymphocytes; helper-inducer; T-lymphocytes; regulatory