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

  • Kumi Mesaki
  • Masaomi YamaneEmail author
  • Seiichiro Sugimoto
  • Masayoshi Fujisawa
  • Teizo Yoshimura
  • Takeshi Kurosaki
  • Shinji Otani
  • Shinichiro Miyoshi
  • Takahiro Oto
  • Akihiro Matsukawa
  • Shinichi Toyooka
Original Article
  • 31 Downloads

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

SOCS3 Th1 Lung transplantation CLAD OB 

Abbreviations

CLAD

Chronic lung allograft dysfunction

CXCL

C-X-C motif chemokine ligand

IL

Interleukin

IFN

Interferon

JAK/STAT

Janus kinase-signal transducer and activator of transcription

OB

Obliterative bronchiolitis

RAG1

Recombination activating 1

SEM

Standard error of the mean

SOCS

Suppressor of cytokine signaling

Th

T helper cell

Treg

Regulatory T cell

Notes

Acknowledgements

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.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Kumi Mesaki
    • 1
  • Masaomi Yamane
    • 1
    Email author
  • Seiichiro Sugimoto
    • 1
  • Masayoshi Fujisawa
    • 2
  • Teizo Yoshimura
    • 2
  • Takeshi Kurosaki
    • 3
  • Shinji Otani
    • 3
  • Shinichiro Miyoshi
    • 1
  • Takahiro Oto
    • 3
  • Akihiro Matsukawa
    • 2
  • Shinichi Toyooka
    • 1
  1. 1.Department of General Thoracic Surgery and Breast and Endocrinological SurgeryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  2. 2.Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  3. 3.Organ Transplant CenterOkayama University HospitalOkayamaJapan

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