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

Abstract

SummaryInterleukin-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 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.

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

“…We hypothesized that the strong anti-inflammatory effect of IL-33 in CIA is in part mediated through Treg expansion and activation. Indeed, our work shows that IL-33 administration in vivo increases the frequency of Tregs, confirming in vitro and in vivo data obtained in three other studies performed in Con Ainduced hepatitis (46) and in allograft models (13,14). It was also shown that IL-33 is a key regulator of intestinal immune response by promoting Tregs in the intestine (47).…”

“…However, a similar amplification of this type 2 immune response, initiated by IL-33, aggravates asthma, which is clearly a Th2-driven disease (12). Moreover, it has recently been shown that IL-33 can activate and promote CD4 + Foxp3 + regulatory T cell (Treg) expansion, thus protecting mice from cardiac or skin transplant rejection (13,14). In this study, we investigated the role of IL-33 in a model of chronic inflammatory arthritis.…”

IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population

“…In this context, it was demonstrated that IL-33 could also expand MDSCs, which in turn generate periphery-induced Foxp3 + Treg cells mediating cardiac and skin allograft survival1852. Moreover, it was reported that an MyD88-dependent MDSC population that express IL-10 expanded after CLP in mice, contributing to the T cell suppression seen after sepsis53.…”

IL-33 enhances retinoic acid signaling on CD4+ T cells

“…Interestingly enough is the fact that RA is involved in Th1, Th2, Th17 and Treg differentiation, affecting a plethora of immunological events. On the other hand, IL-33 has been recently reported as an inducer of Treg cells as well (in vitro and in vivo), adding to the previous data stating that IL-33 may drive either Th1 or Th2 responses [12].…”