title: TLR7 promotes Th1 polarization in immune thrombocytopenia.
abstract: BACKGROUND
  T helper 1 cell (Th1) polarization persists in the autoimmune response found in immune thrombocytopenia (ITP). Toll-like receptor 7 (TLR7) expression, which also plays an important role in autoimmune diseases, was verified to increase in ITP. However, the exact role of TLR7 in ITP is not well elucidated. Here, we explored the hypothesis that TLR7 participates in the pathophysiology of ITP by affecting Th1 polarization.
  
  
  METHODS
  Twenty-two ITP patients and twenty-one controls were enrolled in this study. We examined the cytokine secretion of macrophages in ITP patients and controls using both TLR7 agonist (imiquimod) and antagonist (IRS 661). The influence of macrophage secretion from these groups and its effects on Th1/Th2 differentiation were subsequently studied. Effects of TLR7 on Th1/Th2 balance and platelet counts were also studied in vivo using a thrombocytopenic mouse model.
  
  
  RESULTS
  In in vitro assays, imiquimod enhanced interleukin (IL)-12 secretion in macrophages from ITP patients inducing Th1 differentiation. However, IRS 661 had the exact opposite effect and skewed Th differentiation towards the Th2 subset in ITP. Results from our in vivo studies indicated that injection of imiquimod in ITP mice resulted in elevated plasma levels of IFN-γ and decreased platelet counts. Nevertheless, injection of IRS 661 resulted in elevated plasma levels of IL-4 and platelet counts.
  
  
  CONCLUSIONS
  These findings indicate that TLR7 promotes Th1 polarization and may contribute thus in the pathogenesis of ITP.
authors: Shandong University School of Medicine, Jinan 250012, China.
authors: Qing
authors: Q
authors: Yang
authors: Bo
authors: B
authors: Wang
authors: Huiming
authors: H
authors: Yu
authors: Yuanyuan
authors: Y
authors: Zhu
authors: Xuping
authors: X
authors: Wang
authors: Hong
authors: H
authors: Jiang
authors: Chunyan
authors: C
authors: Wang
authors: Jun
authors: J
authors: Peng
authors: Ming
authors: M
authors: Hou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000097:blood / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7