T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines.
Analysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame of Herpesvirus saimiri. Here we report on the cloning of human IL-17 (hIL-17), the human counterpart of murine IL-17. hIL-17 is a glycoprotein of 155 amino acids secreted as an homodimer by activated memory CD4+ T cells. Although devoid of direct effects on cells of hematopoietic origin, hIL-17 and the product of its viral counterpart, ORF13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte-colony-stimulating factor, as well as prostaglandin E2. Furthermore, when cultured in the presence of hIL-17, fibroblasts could sustain the proliferation of CD34+ hematopoietic progenitors and their preferential maturation into neutrophils. These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.
Fossiez
F
F
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Djossou
O
O
Chomarat
P
P
Flores-Romo
L
L
Ait-Yahia
S
S
Maat
C
C
Pin
J J
JJ
Garrone
P
P
Garcia
E
E
Saeland
S
S
Blanchard
D
D
Gaillard
C
C
Das Mahapatra
B
B
Rouvier
E
E
Golstein
P
P
Banchereau
J
J
Lebecque
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology*; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D020381:Interleukin-17; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011994:Recombinant Proteins / Q000096:biosynthesis; D012016:Reference Values; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000276:immunology; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014764:Viral Proteins / Q000096:biosynthesis / Q000737:chemistry
D016207:Cytokines; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D046911:Macromolecular Substances; C100346:ORF13 protein, Herpesvirus saimiri; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D015232:Dinoprostone