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. 2019 May;49(5):443-450.
doi: 10.1007/s00595-018-1753-5. Epub 2019 Jan 7.

SOCS3 overexpression in T cells ameliorates chronic airway obstruction in a murine heterotopic tracheal transplantation model

Kumi Mesaki  1 , Masaomi Yamane  2 , Seiichiro Sugimoto  1 , Masayoshi Fujisawa  3 , Teizo Yoshimura  3 , Takeshi Kurosaki  4 , Shinji Otani  4 , Shinichiro Miyoshi  1 , Takahiro Oto  4 , Akihiro Matsukawa  3 , Shinichi Toyooka  1
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Free article

SOCS3 overexpression in T cells ameliorates chronic airway obstruction in a murine heterotopic tracheal transplantation model

Kumi Mesaki et al. Surg Today. 2019 May.
Free article

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: CLAD; Lung transplantation; OB; SOCS3; Th1.

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