Increased Th17/Treg ratio in chronic liver GVHD

Abstract

The contribution of Th17 cells to chronic GVHD (cGVHD) has been demonstrated in cGVHD mouse models. However, their contribution to human liver cGVHD remains unclear. We evaluated Th17 cells in biopsies from a cohort of 17 patients with liver cGVHD. We observed a significant increase in Th17 cells in the liver of patients with cGVHD, as demonstrated by an increase in CCR6+, CD161+ and RORγt+ T cells (P=0.03, P=0.0001 and P=0.03, respectively). We also assessed the presence of Th1 and regulatory (Treg) T cells: the numbers of Th1 and Treg cells were very low, with no difference between the two groups (P=0.88 and P=0.12, respectively). Furthermore, Th17/Th1 and Th17/Treg ratios were significantly increased in the liver of patients with liver cGVHD (P=0.005 and P=0.002, respectively). This study provides evidence for an infiltration by Th17 cells in the liver of patients with cGVHD and an increased Th17/Treg ratio, suggesting a defect in the regulatory mechanism driven by Treg cells or an inappropriate activation of effectors cells, especially Th17 cells, or both mechanisms, in human liver cGVHD.

Plasma Kinetics of Th1, Th2 and Th17 Cytokines in Polymyositis Related to Chronic Graft-versus-Host Disease

“…Increasing evidence has shown an association between Th17 cells and various autoimmune diseases (3,7,8). To the best of our knowledge, only two recent clinical studies have reported on the association between Th17 cells and active cGVHD in patients undergoing allo-HCT (9,10). However, this association has not yet been established, and little is known about the balance between and the kinetics of Th1, Th2 and Th17 cells in active cGVHD.…”

“…In contrast, only two recent clinical studies have investigated the association between Th17 cells and cGVHD in transplant patients (9,10 IFN-: interferon-, IP-10: interferon gamma i cible protein-10, MCP-1: monoc te chemoattractant-1, MIP-1 : macrophage inflammator protein-1 , PDGFre lated on activation, normal T cell expressed and secreted, TNF-: t mor necrosis factor-, VEGF: vasc lar endothelial growth factor †For aldolase, the data at da 11 and da were described instead of the data at da 14 and da ‡The 75th percentile data are cited from the plasma data of controls in the Swedish lation-based cohorts (reference 13). For the RANTES data onl the er limit data is cited from the ser m data of healt controls (reference 14).…”

“…Malard et al reported a significant increase in the number of Th17 cells in the liver of cGVHD patients when compared to the patient control group and a very low number of Th1 cells (9). However, it is unknown whether the balance between Th1, Th2 and Th17 cytokines is involved in the development of cGVHD.…”

The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease

“…Several studies showed high expression of pathogenic TH17 in cGVHD patients compared non-GVHD patients [62–64]. Recently, a CD4 T-cell population, expressing CD146, an adhesion molecule and CCR5, a chemokine receptor, was identified in cGVHD patients.…”

Antithymocyte globulin combined with cyclosporine A down-regulates T helper 1 cells by modulating T cell immune response cDNA 7 in aplastic anemia

“…Further studies demonstrated that the antibody against TIRC7 could significantly inhibit the expression of interleukin (IL)-2 and interferon (IFN)-c, without affecting the expression of IL-4, indicating the critical role of TIRC7 in T helper (Th) 1 cells [11]. Regulatory T cells (Tregs) are shown to play the important role in many diseases such as GVHD [12], inflammation of the digestive system [13] and arthritis [14]. Previous study [15] showed that CD25 low TIRC7 ?…”