, Volume 60, Issue 12, pp 2409–2417 | Cite as

Differential modulation of IL-12 family cytokines in autoimmune islet graft failure in mice

  • Feng-Cheng Chou
  • Heng-Yi Chen
  • Hsin-Hui Chen
  • Gu-Jiun Lin
  • Shih-Hua Lin
  • Huey-Kang Sytwu



The relative contribution of T helper (Th)1 and Th17 cells in graft rejection is inconclusive, on the basis of evidence provided by different T cell-related cytokine-deficient animal models and graft types.


We used novel antigen-presenting-cell-specific Il-12p35 (also known as Il12a)-knockout (KO), IL-23p19-knockdown (KD) and IL-27p28-KD strategies to investigate T cell differentiation in islet graft rejection.


In vitro dendritic cell–T cell coculture experiments revealed that dendritic cells from Il-12p35-KO and IL-23p19-KD mice showed reduced ability to stimulate IFN-γ and IL-17 production in T cells, respectively. To further explore the T cell responses in islet graft rejection, we transplanted islets into streptozotocin-induced diabetic NOD/severe combined immunodeficiency (SCID) recipient mice with IL-12-, IL-23-, or IL-27-deficient backgrounds and then challenged them with NOD.BDC2.5 T cells. The survival of islet grafts was significantly prolonged in Il-12p35-KO and IL-23p19-KD recipients compared with the control recipients. T cell infiltrations and Th1 cell populations were also decreased in the grafts, correlating with prolonged graft survival.


Our results suggest that IL-12 and IL-23 promote and/or maintain Th1 cell-mediated islet graft rejection. Thus, blockade of IL-12 and IL-23 might act as therapeutic strategies for reducing rejection responses.


Graft rejection IL-12 IL-23 Islet transplantation Th1 Th17 



Antigen-presenting cell


Bone-marrow-derived dendritic cell


Graft-infiltrating cell






Pancreatic lymph node


Pattern-recognition receptor


Severe combined immunodeficiency


T helper


Toll-like receptor


Regulatory T





Some of the data were presented as an abstract at the 63rd Annual Meeting of the Japanese Association for Laboratory Animal Science, 18–20 May 2016, Kawasaki, Japan, and the 16th International Congress of Immunology, 21–26 August 2016, Melbourne, Australia.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.


This work was supported by the Ministry of Science and Technology (MOST), Taiwan, Republic of China. (MOST 103-2320-B-016-017-MY3 and MOST 104-2320-B-016-014-MY3 to HKS; NSC 102-2321-B-016-005-MY3 to FCC), Tri-Service General Hospital Foundation (TSGH-C106-004-006-008-S02 to HKS), and Tri-Service General Hospital (VTA106-T-1-1 to HKS).

Duality of interest

The authors confirm that there is no duality of interest associated with this manuscript.

Contribution statement

FCC, HYC, HHC, GJL, SHL and HKS contributed to conception and design, acquisition of data or analysis and interpretation of data. All authors drafted the article and/or revised it critically for important intellectual content. All authors approved the final version to be published. FCC and HKS are responsible for the integrity of the work as a whole.

Supplementary material

125_2017_4418_MOESM1_ESM.pdf (437 kb)
ESM (PDF 436 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Feng-Cheng Chou
    • 1
  • Heng-Yi Chen
    • 2
  • Hsin-Hui Chen
    • 3
  • Gu-Jiun Lin
    • 4
  • Shih-Hua Lin
    • 5
  • Huey-Kang Sytwu
    • 1
    • 2
  1. 1.Department and Graduate Institute of Microbiology and ImmunologyNational Defense Medical CenterTaipei 114Taiwan
  2. 2.Graduate Institute of Life SciencesNational Defense Medical CenterTaipeiTaiwan
  3. 3.Department of MedicineNational Defense Medical CenterTaipeiTaiwan
  4. 4.Department of Biology and AnatomyNational Defense Medical CenterTaipeiTaiwan
  5. 5.Department of Internal MedicineTri-Service General Hospital, National Defense Medical CenterTaipeiTaiwan

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