SOCS3 overexpression in T cells ameliorates chronic airway obstruction in a murine heterotopic tracheal transplantation model
Suppressor of cytokine signaling-3 (SOCS3) is a negative feedback inhibitor of cytokine signaling with T-cell-mediated immunosuppressive effects on obliterative bronchiolitis (OB). In this study, we aimed to investigate the impact of T-cell-specific overexpression of SOCS3 using a murine heterotopic tracheal transplantation (HTT) model.
Tracheal allografts from BALB/c mice were subcutaneously transplanted into wild-type C57BL/6J (B6; WT) mice and SOCS3 transgenic B6 (SOCS3TG) mice. Tracheal allografts were analyzed by immunohistochemistry and quantitative polymerase chain reaction assays at days 7 and 21.
At day 21, allografts in SOCS3TG mice showed significant amelioration of airway obstruction and epithelial loss compared with allografts in WT mice. The intragraft expression of IFN-γ and CXCL10 was suppressed, while that of IL-4 was enhanced in SOCS3TG mice at day 7. The T-bet levels were lower in SOCS3TG allografts than in WT allografts at day 7.
We revealed that the overexpression of SOCS3 in T cells effectively ameliorates OB development in a murine HTT model by inhibiting the Th1 phenotype in the early phase. Our results suggest that the regulation of the T-cell response, through the modulation of SOCS expression, has potential as a new therapeutic strategy for chronic lung allograft dysfunction.
KeywordsSOCS3 Th1 Lung transplantation CLAD OB
Chronic lung allograft dysfunction
C-X-C motif chemokine ligand
Janus kinase-signal transducer and activator of transcription
Recombination activating 1
Standard error of the mean
Suppressor of cytokine signaling
T helper cell
Regulatory T cell
We would like to thank Mr. Haruyuki Watanabe from the Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, for his great technical assistance.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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