Exogenous interleukin-33 targets myeloid-derived suppressor cells and generates periphery-induced Foxp3+ regulatory T cells in skin-transplanted mice

Tania Gajardo, Rodrigo A. Morales, Mauricio Campos-Mora, Javier Campos-Acuña, Karina Pino-Lagos

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Interleukin-33 (IL-33) has been a focus of study because of its variety of functions shaping CD4+ T-cell biology. In the present work, we evaluated the modulatory effect of IL-33 on suppressor cells in an in vivo transplantation model. C57BL/6 wild-type mice were grafted with syngeneic or allogeneic skin transplants and treated with exogenous IL-33 daily. After 10 days of treatment, we analysed draining lymph node cellularity and found in allogeneic animals an increment in myeloid-derived suppressor cells, which co-express MHC-II, and become enriched upon IL-33 treatment. In line with this observation, inducible nitric oxide synthase and arginase 1 expression were also increased in allogeneic animals upon IL-33 administration. In addition, IL-33 treatment up-regulated the number of Foxp3+ regulatory T (Treg) cells in the allogeneic group, complementing the healthier integrity of the allografts and the increased allograft survival. Moreover, we demonstrate that IL-33 promotes CD4+ T-cell expansion and conversion of CD4+ Foxp3- T cells into CD4+ Foxp3+ Treg cells in the periphery. Lastly, the cytokine pattern of ex vivo-stimulated draining lymph nodes indicates that IL-33 dampens interferon-γ and IL-17 production, stimulating IL-10 secretion. Altogether, our work complements previous studies on the immune-modulatory activity of IL-33, showing that this cytokine affects myeloid-derived suppressor cells at the cell number and gene expression levels. More importantly, our research demonstrates for the first time that IL-33 allows for in vivo Foxp3+ Treg cell conversion and favours an anti-inflammatory or tolerogenic state by skewing cytokine production. Therefore, our data suggest a potential use of IL-33 to prevent allograft rejection, bringing new therapeutics to the transplantation field.

Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalImmunology
Volume146
Issue number1
DOIs
StatePublished - 1 Sep 2015

Bibliographical note

Publisher Copyright:
© 2015 John Wiley & Sons Ltd.

Keywords

  • Foxp3 regulatory T cells
  • Interleukin-33
  • Tolerance
  • Transplantation

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