RT Journal Article
SR Electronic
T1 HCMV infection triggers the development of interstitial lung diseases in autoimmune disorders
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 4632
VO 44
IS Suppl 58
A1 Jun Xu
A1 Wei Wang
A1 Qun Luo
A1 Rong-Chang Chen
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/4632.abstract
AB Rationale: Interstitial lung disease in connective tissue diseases (CTD-ILD) is a leading cause of death in these patients. However, the pathogenesis of ILD development in these patients remains unclear, although human cytomegalovirus (HCMV) microinfections have been associated with inflammatory diseases.Objectives: To determine the role of HCMV infection in the initiation of ILD in CTD-ILD patients.Methods: Herpes virus (HCMV, EBV, and HSV) DNA was tested by real-time PCR in the peripheral blood mononuclear cells (PBMCs), plasma and lung biopsies of 62 patients with CTD-ILD, 16 patients with CTD(rheumatoid arthritis RA) without ILD and 33 healthy controls. The T lymphocyte subsets and cytokine profile were analyzed by flow cytometry and liquid Chip.Main Results: The detection rate of HCMV was remarkably higher in patients with CTD-ILD regardless of being treated with immunosuppressors, than in either healthy controls or RA patients. HCMV infection was closely relevant to the increased frequency of CD3+CD8+T cells accompanied by the reduced regulatory T cell (Tregs) level, and to markedly increased IL-6 level with decreased TGF-β1 to IL-6 ratio, which correlated highly with the preceding parameters of disease severity. HCMV clearance contributed to significantly improved parameters of ILD severity in the patients during a 6 month follow-up after treatment. Human lung fibroblasts co-cultured with HCMV-infected PBMCs showed a remarkable increase of IL-6 expression, which is associated with an aberrant IL-6 dependent Stat3 signal that promotes myofibroblast activation.Conclusions: HCMV induces pulmonary fibrogenesis in autoimmunity throughout triggering an excessive IL-6 signaling.