IL‐33 broadens its repertoire to affect DC

IL‐33 is a novel multi‐functional IL‐1 family member that, in contrast to other family members, is associated with Th2 responses. IL‐33 signals via a heterodimer composed of its receptor, IL‐1 receptor‐like‐1 (IL‐1RL1), more commonly known as ST2L, and the IL‐1R accessory protein. ST2L is expressed by endothelial cells, mast cells, basophils, Th2 cells, and DC. IL‐33 has been associated with several immune‐mediated disorders, including asthma, arthritis, and inflammatory bowel disease. In contrast, there is evidence that IL‐33 can inhibit atherosclerosis development. A report in this issue of the European Journal of Immunology reveals a novel function of IL‐33: the ability to promote myeloid DC generation in murine BM cell cultures, by triggering GM‐CSF production by other BM cells, likely basophils. DC generated in the presence of IL‐33 are maturation resistant, with only minimal T‐cell stimulatory ability, associated with comparatively high levels of programmed death receptor ligand expression. This commentary discusses several questions raised by these findings, and provides a basis for further evaluation of IL‐33 and ST2L in regulation of APC generation and function in both innate and adaptive immunity.