title: Human eosinophils produce the T cell-attracting chemokines MIG and IP-10 upon stimulation with IFN-gamma.
abstract: Eosinophils participate in allergic inflammation, where expression of T helper cell type 2 (Th2) cytokines such as interleukin (IL)-4 and IL-5 are seen. However, eosinophils sometimes accumulate during disease with expression of Th1 cytokines [i.e., interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-1beta]. In this study, we investigated whether eosinophils can respond with expression of the IFN-inducible C-X-C chemokines monokine induced by IFN-gamma [MIG; CXC chemokine ligand 9 (CXCL9)], IFN-gamma-inducible protein (IP-10/CXCL10), and IFN-inducible T cell alpha chemoattractant (I-TAC/CXCL11). These chemokines share the ability to recruit and activate T cells and natural killer cells to sites of inflammation. We found that IFN-gamma induced rapid and sustained gene expression of MIG, IP-10, and I-TAC in eosinophils, as detected by quantitative reverse transcriptase-polymerase chain reaction. During incubation, IFN-gamma-stimulated eosinophils released MIG and IP-10, as detected by enzyme-linked immunosorbent assay, while I-TAC could not be detected in the medium. TNF-alpha but not IL-1beta enhanced the IFN-gamma-induced production of MIG and IP-10. Conversely, addition of the Th2 cytokine IL-4 down-regulated IFN-gamma-induced synthesis of MIG and IP-10 in eosinophils. Crohn's disease is characterized by a Th1-polarized inflammation and presence of eosinophils. In lesions from this disease, MIG was detected in eosinophils by immunohistochemistry. Taken together, the results point to immunoregulatory roles for eosinophils during some diseases with Th1-polarized inflammation.
authors.affiliation: Department of Medical Microbiology, Malmö University Hospital, Tornavägen 10, SE-221 84 Lund, Sweden.
authors.forename: Terese
authors.initials: T
authors.lastname: Dajotoy
authors.forename: Pia
authors.initials: P
authors.lastname: Andersson
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Löfdahl
authors.forename: Hans
authors.initials: H
authors.lastname: Tapper
authors.forename: Arne
authors.initials: A
authors.lastname: Egesten
mesh_terms: D002460:Cell Line; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
chemical_list: C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma