T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines.

Abstract

SummaryAnalysis 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 ofHerpesvirus saimiri. Here we report on the cloning of human , the human counterpart ofmurine IL-17. hlL-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, hlL-17 and the product of its viral counterpart, Olq.F13, 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 hlL-17, fibroblasts could sustain the proliferation of CD34 + hematopoietic progenitors and their preferential maturation into neutrophils. These observations suggest that hlL-17 may constitute (a) an early initiator of the T cell-dependent inflammatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.T lymphocytes produce an array of small proteins that are involved in cell growth, inflammation, immunity, differentiation, and repair. These protein mediators referred to as cytokines are not produced constitutively by T cells, but rather are induced after receptor-mediated T cell activation (1, 2). Murine cytotoxic T lymphocyte associated antigen-8 (mCTLA8) 1, a cDNA previously cloned by lq.ouvier et al. (3) from a T cell subtraction library, displays some of the features ofa cytokine gene: in particular, a pre1Abbreviations used in this paper: hlL-17, human IL-17; HVS, Herpesvirus saimiri; ORF13, open reading frame 13; mCTLA8, murine cytotoxic T lymphocyte-associated antigen 8; PGE 2, prostaglandin E2; PI, PMA and ionomycin.Parts of this work were presented at

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

“…GM-CSF can promote granulopoiesis [9,10], and has been implicated in protection against L. monocytogenes infection [74]. IL-17 plays a crucial role in induction of G-CSF [9,10,[15][16][17][18], and has also been implicated in protection against L. monocytogenes infection [67,75]. Therefore, we next examined whether infiltration of Gr-1 1 cells into the liver following a-GalCer treatment is caused by GM-CSF and/or IL-17.…”

“…Numerous cytokines such as GM-CSF, IL-3, IL-6, IL-11, and SCF promote granulopoiesis by themselves and/or in concert with G-CSF [9,10]. G-CSF is indispensable for both steady-state and emergency granulopoiesis [11][12][13][14], and IL-17 regulates G-CSF secretion [9,10,[15][16][17][18]. In addition to Gr-1 1 cells, g/d T cells also participate in early protection against L. monocytogenes infection [19][20][21][22].…”

Treatment with a neutralizing anti‐murine interleukin‐17 antibody after the onset of collagen‐induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

“…Interleukin-17 (IL-17) is a T cell-derived cytokine produced by activated T cells, predominantly activated CD4ϩ,CD45ROϩ memory T cells (1,2). This cytokine may play a role in T cell-triggered inflammation by stimulating stromal cells to secrete various cytokines and growth factors associated with inflammation (1)(2)(3)(4).…”

“…This cytokine may play a role in T cell-triggered inflammation by stimulating stromal cells to secrete various cytokines and growth factors associated with inflammation (1)(2)(3)(4). A pathogenic role for IL-17 was found in organ allograft rejection (5), and increased IL-17 expression was detected in several diseases, such as systemic sclerosis (6), nephrotic syndrome (7), systemic lupus erythematosus (8), and rheumatoid arthritis (RA) (9,10).…”

“…IL-17 can stimulate the production of IL-1␤ and TNF␣ from macrophages (4) and triggers human synoviocytes to produce IL-6, IL-8, granulocytemacrophage colony-stimulating factor, and prostaglandin E 2 (2,16), suggesting that IL-17 could be an upstream mediator in the pathogenesis of arthritis. Early neutralization of endogenous IL-17 prior to the development of arthritis in the experimental arthritis model suppresses the onset of disease (17,18).…”