The role of IL-23/Th17 pathway in patients with primary immune thrombocytopenia

PLoS One. 2015 Jan 26;10(1):e0117704. doi: 10.1371/journal.pone.0117704. eCollection 2015.

Abstract

Background: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an unclear etiology. This study aims to investigate the role of IL-23/Th17 pathway in patients with ITP.

Method: The gene expressions of IL-17, IL-23 and their receptors in ITP patients and healthy controls were analyzed by quantitative real-time PCR. ELISA was used to test the IL-17 and IL-23 levels in plasma. Flow cytometry was used to detect the frequency of Th17 cells. The correlation between plasma IL-23 and IL-17 levels, Th17 cells, platelets were analyzed. The level of Th17-related cytokines was measured by ELISA following stimulation with IL-23. Subsequently, the IL-23 and IL-17 levels were measured in patients post-treatment.

Results: The PBMCs of ITP patients showed increased mRNA expression levels in each of the following: IL-23p19, IL-12p40, IL-23R, IL-12Rβ1, IL-17A, IL-17F, and RORC. In addition, elevated Th17 cells and plasma IL-17, IL-23 levels were also observed in these ITP patients. Furthermore, it was found that IL-23 levels in plasma are positively correlated with IL-17 levels and Th17 cells, yet negatively correlated with platelet count. Following IL-23 stimulation in vitro, IL-17 levels showed significant elevation. Furthermore, both IL-23 and IL-17 levels decreased after effective treatment.

Conclusion: The IL-23/Th17 pathway may be involved in the pathogenesis of ITP through enhancement of the Th17 response. Moreover, our results suggest that the IL-23/Th17 pathway is a potential therapeutic target in future attempts of ITP treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Cells, Cultured
  • Dexamethasone / therapeutic use
  • Female
  • Gene Expression
  • Glucocorticoids / therapeutic use
  • Humans
  • Interleukin-17 / blood
  • Interleukin-17 / genetics
  • Interleukin-23 / blood*
  • Interleukin-23 / genetics
  • Male
  • Middle Aged
  • Platelet Count
  • Purpura, Thrombocytopenic, Idiopathic / blood*
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic / immunology
  • Th17 Cells / physiology*
  • Young Adult

Substances

  • Glucocorticoids
  • Interleukin-17
  • Interleukin-23
  • Dexamethasone

Grants and funding

This research was supported by grants from 973 Foundation (2013CB531606), National Science Foundation of China (81273282, 81202353, 81371786, 81302579), Shanghai Municipal Commission for Science and Technology (11JC1410902), Changhai Hospital (CH125530300), Grant of Nanjing District (12MA056), The Educational reform fund of SMMU, The master’s fund of SMMU graduate school. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.