The Reparative Roles of IL-33.

When discovered in the early 2000s, interleukin-33 (IL-33) was characterized as a potent driver of type 2 immunity and implicated in parasite clearance, as well as asthma, allergy, and lung fibrosis. Yet research in other models has since revealed that IL-33 is a highly pleiotropic molecule with diverse functions. These activities are supported by elusive release mechanisms and diverse expression of the IL-33 receptor, STimulation 2 (ST2), on both immune and stromal cells. Interestingly, IL-33 also supports type 1 immune responses during viral and tumor immunity and after allogeneic hematopoietic stem cell transplantation. Yet the IL-33-ST2 axis is also critical to the establishment of systemic homeostasis and tissue repair and regeneration. Despite these recent findings, the mechanisms by which IL-33 governs the balance between immunity and homeostasis or can support both effective repair and pathogenic fibrosis are poorly understood. As such, ongoing research is trying to understand the potential reparative and regulatory versus pro-inflammatory and pro-fibrotic roles for IL-33 in transplantation. This review provides an overview of the emerging regenerative role of IL-33 in organ homeostasis and tissue repair as it relates to transplantation immunology. It also outlines the known impacts of IL-33 in commonly transplanted solid organs and covers the envisioned roles for IL-33 in ischemia-reperfusion injury, rejection, and tolerance. Finally, we give a comprehensive summary of its effects on different cell populations involved in these processes, including ST2 + regulatory T cells, innate lymphoid cell type 2, as well as significant myeloid cell populations.

Antigen-specific B cells in kidney transplantation.

In this issue, Burton et al. describe a convincing method to identify and enumerate human leukocyte antigen-specific B cells and subsets using biotinylated human leukocyte antigen proteins. Importantly, they demonstrate that these antigen-specific B cells are found at a greater frequency in sensitized kidney transplant recipients when compared with healthy volunteers. Finally, using an indirect antigen-specific enzyme-linked immunosorbent spot assay, they uncover the complexity of B- and T-cell interactions and the influence of regulatory T cells on such interactions in vitro.