The short form of TSLP is constitutively translated in human keratinocytes and has characteristics of an antimicrobial peptide.
Thymic stromal lymphopoietin (TSLP) has multifaceted immunological functions ranging from maintenance of tolerance to induction of disease. Two human transcript variants of TSLP are described: a long form (variant 1; lfTSLP) consisting of four exons and an alternative, short form (variant 2; sfTSLP) that lacks two exons compared with variant 1. SfTSLP has not been described at the protein level or functionally studied. Here, we demonstrate that the human sfTSLP is the predominant form of TSLP, constitutively expressed at the mRNA and protein level in keratinocytes of oral mucosa and skin and in salivary glands, is released in saliva, and is not regulated in the same manner as the long form. Compared with lfTSLP, sfTSLP exhibits a markedly stronger antibacterial activity. Synthetic sfTSLP did not activate signal transducer and activator of transcription 5 (STAT5) signaling in CD1c(+) dendritic cells nor interfered with STAT5 activation by lfTSLP. SfTSLP may, therefore, act as an antimicrobial peptide in the oral cavity and on the skin to create a defense barrier that aids in the control of both commensal and pathogenic microbes. The results show that the two translational products of the TSLP gene have a different expression and different biological properties, and emphasize the importance of analyzing the two TSLP isoforms separately.
Department of Oral Biology, Dental Faculty, University of Oslo, Oslo, Norway.
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L
Bjerkan
Department of Oral Biology, Dental Faculty, University of Oslo, Oslo, Norway.
O
O
Schreurs
Department of Oral Biology, Dental Faculty, University of Oslo, Oslo, Norway.
S A
SA
Engen
Centre for Immune Regulation and Department of Pathology, Medical Faculty, University of Oslo, Oslo, Norway.
F L
FL
Jahnsen
Centre for Immune Regulation and Department of Pathology, Medical Faculty, University of Oslo, Oslo, Norway.
E S
ES
Baekkevold
1] Department of Oral Biology, Dental Faculty, University of Oslo, Oslo, Norway [2] Department of Periodontology, Dental Faculty, University of Oslo, Oslo, Norway.
I J S
IJ
Blix
Department of Oral Biology, Dental Faculty, University of Oslo, Oslo, Norway.
K
K
Schenck
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D005658:Fungi / Q000187:drug effects* / Q000254:growth & development; D005786:Gene Expression Regulation; D006801:Humans; D018928:Immunity, Mucosal; D015603:Keratinocytes / Q000276:immunology*; D009061:Mouth Mucosa / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012469:Salivary Glands / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D020033:Protein Isoforms; D050799:STAT5 Transcription Factor; D000094632:Thymic Stromal Lymphopoietin