title: T cell-derived microvesicles induce mast cell production of IL-24: relevance to inflammatory skin diseases.
abstract: BACKGROUND
  It has recently been shown that microvesicles derived from activated T cells can stimulate human mast cells (MCs) to degranulate and release several cytokines.
  
  
  OBJECTIVE
  The aim of this study was to characterize microvesicle-induced MC expression patterns. Through identification of unique cytokine and chemokine expression, we attempted to reveal pathogenetic roles for this pathway of MC activation.
  
  
  METHODS
  T cell-derived microvesicles were labeled with PKH67 to allow visualization of their interaction with human MCs. Consequent gene expression profiling was studied by using a whole-genome microarray and analyzed for identification of cellular pathway clusters. Expression of 3 selected genes, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 7 (CCL7), and IL24, was validated by means of quantitative RT-PCR and specific ELISA. IL24, which has not been recognized heretofore in MCs, was also tested for its effect on keratinocyte signal transducer and activator of transcription 3 phosphorylation and for its presence in MCs in psoriatic skin lesions.
  
  
  RESULTS
  Uptake and internalization of activated T cell-derived microvesicles into human MCs occurred within 24 hours. Microvesicles induced the upregulation of several clusters of genes, notably those that are cytokine related. Among these, IL24 appeared to be a hallmark of microvesicle-induced activation. MC-derived IL-24, in turn, activates keratinocytes in vitro, as manifested by signal transducer and activator of transcription 3 (STAT3) phosphorylation, and is produced in MCs within psoriatic lesions.
  
  
  CONCLUSIONS
  Production of IL-24 is a unique feature of microvesicle-induced MC activation because its production by these cells has not been recognized thus far. We propose that this MC-derived cytokine might contribute to the pathologic findings in T cell-mediated skin inflammation.
authors.affiliation: Laboratory of Allergy and Clinical Immunology, Meir General Hospital, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Shefler
authors.affiliation: Bioinformatics unit, G.S Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.affiliation: Department of Pathology, Meir General Hospital, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Dvora
authors.initials: D
authors.lastname: Kidron
authors.affiliation: Laboratory of Allergy and Clinical Immunology, Meir General Hospital, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ymekori@clalit.org.il.
authors.forename: Yoseph A
authors.initials: YA
authors.lastname: Mekori
authors.affiliation: Laboratory of Allergy and Clinical Immunology, Meir General Hospital, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Alon Y
authors.initials: AY
authors.lastname: Hershko
mesh_terms: D015550:Cell Degranulation; D002460:Cell Line; D002469:Cell Separation; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D054410:Chemokine CCL7 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D046228:Microarray Analysis; D009930:Organic Chemicals / Q000378:metabolism; D010766:Phosphorylation; D011565:Psoriasis / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D000099180:Interleukin-24
chemical_list: D054405:Chemokine CCL3; D054410:Chemokine CCL7; D007378:Interleukins; D009930:Organic Chemicals; D050796:STAT3 Transcription Factor; D000099180:Interleukin-24; C451241:PKH67
keywords: CCL3; CCL7; Chemokine (C-C motif) ligand 3; Chemokine (C-C motif) ligand 7; ERK; Extracellular signal-regulated kinase; IL-24; JNK; Jun N-terminal kinase; MAPK; MC; Mast cell; Microvesicles derived from activated T cells; Microvesicles derived from resting T cells; Mitogen-activated protein kinase; STAT3; Signal transducer and activator of transcription 3; T cells; mast cells; microvesicles; mvT; mvT*