title: Making many from few: IL-12p40 as a model for the combinatorial assembly of heterodimeric cytokines.
abstract: How dendritic cells (DCs) gather information from the local milieu at a site of infection or injury and communicate this to influence adaptive immunity is not well understood. We and others have reported that soon after microbial encounter, DCs secrete the p40 subunit of IL-12, by itself, in a monomeric form. Based on recent data that this p40 monomer subsequently associates with p35 released from other cells to generate functional IL-12, we proposed that p40 can function as a DC-derived probe which samples the composition of the local milieu by looking for other binding partners. In this opinion, we discuss how such a sampling function might generate an elaborate combinatorial "code" of heterodimeric cytokines, capable of conveying location-specific information to cells downstream of DC activation, including NK and T cells.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II 12441 Parklawn Dr., Rockville, MD 20852, United States.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Abdi
authors.affiliation: Department of Microbiology & Immunology, University of Maryland School of Medicine, 685 W Baltimore St, HSF1, Room 380, Baltimore, MD 21201, United States. Electronic address: nsingh@som.umaryland.edu.
authors.forename: Nevil J
authors.initials: NJ
authors.lastname: Singh
mesh_terms: D000818:Animals; D016207:Cytokines / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D055503:Protein Multimerization; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D018664:Interleukin-12
keywords: Dendritic cells; Hypothesis; IL-12; Immunological class; Innate activation; T cell differentiation; Tissue immunity