title: Interleukin-4 induced interferon regulatory factor (Irf) 4 participates in the regulation of alternative macrophage priming.
abstract: Interleukin (IL)-4 is a central regulator of T helper 2 (Th2) immune responses, and also has a major impact on innate immune cells. This cytokine primes macrophages for immune responses to parasites and induces a distinct macrophage phenotype that may also promote tissue repair. IL-4 signaling in macrophages is primarily mediated by the transcription factor signal transducer and activator of transcription 6 (Stat6), which in turn regulates a number of secondary DNA binding proteins that may participate in shaping the resulting phenotype. The impact of secondary transcription factors on IL-4-treated macrophages, however, is largely unknown. Here we show that interferon regulatory factor 4 (Irf4) is strongly induced on RNA and protein level in bone marrow-derived macrophages upon priming with IL-4. Using microarray-based whole genome expression analysis, we also demonstrate that a subset of IL-4 regulated genes, including several MHC-II genes, Ciita, Cyp1b1, and Il1rn, are dysregulated in Irf4-deficient macrophages. The presented data suggests a non-redundant role for Irf4 in shaping the phenotype of alternatively primed macrophages.
authors.affiliation: Department of Haematology and Oncology, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Carol
authors.initials: C
authors.lastname: El Chartouni
authors.forename: Lucia
authors.initials: L
authors.lastname: Schwarzfischer
authors.forename: Michael
authors.initials: M
authors.lastname: Rehli
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000235:genetics; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1; D050835:Interferon Regulatory Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D015847:Interleukin-4; D009687:Nuclear Proteins; D050800:STAT6 Transcription Factor; D015534:Trans-Activators; D000099218:Interferon Regulatory Factor-4; C083728:MHC class II transactivator protein; C585498:Cyp1b1 protein, mouse