Abstract
BackgroundChemokines and chemokine receptors play important roles in autoimmune diseases; however, their role in immune thrombocytopenia (ITP) is unclear. High-dose dexamethasone (HD-DXM) may become a first-line therapy for adult patients with ITP, but the effect of HD-DXM on chemokines in ITP patients is unknown. Our aim was to investigate the mechanism of pulsed HD-DXM for management of ITP, specifically regarding the chemokine pathways.MethodsTh1-/Th2-associated chemokine and chemokine receptor profiles in ITP patients before and after pulsed HD-DXM was studied. Plasma levels of CCL5 and CXCL11 (Th1-associated) and of CCL11 (Th2-associated) were determined by ELISA. Gene expression of these three chemokines and their corresponding receptors CCR5, CXCR3, and CCR3, in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR.ResultsThirty-three of the thirty-eight ITP patients responded effectively to HD-DXM (oral, 40 mg/day, 4 days). In ITP patients, plasma CXCL11 levels increased, while CCL11 and CCL5 decreased compared to controls (P < 0.05). Similarly, gene expression of CXCL11 and its receptor CXCR3 increased, while CCL11 and CCR3 decreased (P < 0.05). CCL5 expression did not significantly change; however, expression of its receptor CCR5 increased (P < 0.05). Interestingly, in the patients who responded to pulsed HD-DXM, CXCL11 and CXCR3 expression was down-regulated, while CCL11 and CCR3 expression was up-regulated (P < 0.05). Meanwhile, CCL5 expression was up-regulated and CCR5 was down-regulated by HD-DXM (P < 0.05).ConclusionsThe abnormal profiles of Th1-/Th2-associated chemokines and chemokine receptors may play important roles in the pathogenesis of ITP. Importantly, regulating Th1 polarization by pulsed HD-DXM may represent a novel approach for immunoregulation in ITP.
Highlights
Chemokines and chemokine receptors play important roles in autoimmune diseases; their role in immune thrombocytopenia (ITP) is unclear
By characterizing T-helper 1 (Th1)-associated chemokine receptors CXCR3 and CCR5, and Th2-associated chemokine receptor CCR3, we demonstrated that the abnormal expression of Th1/Th2 chemokine receptors may participate in the splenic immune dysregulation in ITP patients [18]
Plasma levels of CCL5, CXCL11, and CCL11 Compared to normal controls, plasma CCL5 levels were reduced in the active ITP group (126.18 ± 19.84 vs 455.54 ± 68.29 pg/mL)
Summary
Chemokines and chemokine receptors play important roles in autoimmune diseases; their role in immune thrombocytopenia (ITP) is unclear. Immune thrombocytopenia (ITP) is an acquired autoimmune-mediated bleeding disorder, mainly characterized by anti-platelet antibody-mediated thrombocytopenia. Chemokines and their receptors are involved in cellular migration and proliferation, molecule adhesion, Liu et al J Transl Med (2016) 14:301 regulation of apoptosis, T cell differentiation, leukocyte trafficking, and cytokine production [4]. Chemokine CCL5 is required for attracting CCR5+ T cells but is essential for their activation [5]. CCR5 is expressed on Th1 cells and has been reported as a critical chemokine receptor in several autoimmune diseases with polarization of Th1 cells such as rheumatoid arthritis, multiple sclerosis, Crohn’s disease and oral lichen planus [6,7,8]. By characterizing Th1-associated chemokine receptors CXCR3 and CCR5, and Th2-associated chemokine receptor CCR3, we demonstrated that the abnormal expression of Th1/Th2 chemokine receptors may participate in the splenic immune dysregulation in ITP patients [18]
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