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.
Turnquist
Hēth R
HR
Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Thomson
Angus W
AW
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000494:pharmacology*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction
D039521:CD11c Antigen; D016207:Cytokines; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor