title: Interleukin 33 is a guardian of barriers and a local alarmin.
abstract: Interleukin 33 (IL-33) is a member of the IL-1 family of cytokines with a growing number of target cells and a plethora of biological functions. Although it has commonalities with other IL-1 cytokines, IL-33 exhibits some unique features. Here we review the biology of IL-33 and its receptor and develop a working model that describes two 'lives' for IL-33-one intracellular and one extracellular. Under healthy conditions, constitutively produced, intracellular IL-33 participates in maintaining barrier function by regulating gene expression as a nuclear protein. In parallel, nuclear IL-33 functions as a stored alarmin that is released when barriers are breached. Extracellular IL-33 coordinates immune defense and repair mechanisms while also initiating differentiation of helper T cells as the adaptive immune response is triggered.
authors.affiliation: Institute of Cellular Chemistry, Center for Biochemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Nikolas T
authors.initials: NT
authors.lastname: Martin
authors.affiliation: Immunology FB08, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Michael U
authors.initials: MU
authors.lastname: Martin
mesh_terms: D000067531:Alarmins / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000067531:Alarmins; D000067596:Interleukin-33; D018123:Receptors, Interleukin