title: Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions.
abstract: IL-36α, IL-36β, and IL-36γ are members of the IL-1 family of cytokines that signal through a common receptor composed of IL-36R and IL-1R/AcP to activate NF-κB and MAPKs, such as p38 and JNK, and promote inflammatory responses. IL-36Ra is a natural antagonist of the 3 IL-36 agonists that binds to IL-36R and inhibits binding of the agonistic ligands. These cytokines are expressed predominantly by epithelial cells and act on a number of cells, including immune cells, epithelial cells, and fibroblasts. Processing of the N terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been demonstrated extensively in the skin, where it can act on keratinocytes and immune cells to induce a robust inflammatory response and is implicated strongly through functional and genetic evidence in the pathology of psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary physiology and pathology. Although much has been learned about the biochemistry of IL-36 and its role in various tissues, it is clear that we are at an early stage in our understanding of the full biology of these cytokines.
authors: *Division of Rheumatology, Departments of Internal Medicine Specialties and Pathology-Immunology, University Hospitals of Geneva and University of Geneva, Switzerland; and Department of Inflammation Research, Amgen, Seattle, Washington, USA.
authors: Cem
authors: C
authors: Gabay
authors: *Division of Rheumatology, Departments of Internal Medicine Specialties and Pathology-Immunology, University Hospitals of Geneva and University of Geneva, Switzerland; and Department of Inflammation Research, Amgen, Seattle, Washington, USA jtowne1@its.jnj.com.
authors: Jennifer E
authors: JE
authors: Towne
mesh_terms: D000818:Animals; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007375:Interleukin-1 / Q000819:agonists / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053577:Interleukin-1 Receptor Accessory Protein / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology; D020935:MAP Kinase Signaling System; D051379:Mice; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational; D011565:Psoriasis / Q000503:physiopathology; D018123:Receptors, Interleukin / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D016328:NF-kappa B; D018123:Receptors, Interleukin; C572887:interleukin 36, human; C571244:interleukin-36 receptor, human
keywords: IL-1 family; inflammation; lung; psoriasis