Journal ArticleDOI
Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity
Samy Ashkar,Georg F. Weber,Vassiliki Panoutsakopoulou,Marie E. Sanchirico,Marianne Jansson,Samer Zawaideh,Susan R. Rittling,David T. Denhardt,Melvin J. Glimcher,Harvey Cantor +9 more
TLDR
Findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.Abstract:
Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. Mice deficient in Eta-1 (also called osteopontin) gene expression have severely impaired type-1 immunity to viral infection [herpes simplex virus–type 1 (KOS strain)] and bacterial infection ( Listeria monocytogenes ) and do not develop sarcoid-type granulomas. Interleukin-12 (IL-12) and interferon-γ production is diminished, and IL-10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.read more
Citations
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The extracellular matrix: A dynamic niche in cancer progression
TL;DR: The extracellular matrix (ECM), a complex network of macromolecules with distinctive physical, biochemical, and biomechanical properties, is commonly deregulated and becomes disorganized in diseases such as cancer.
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The stem-cell niche as an entity of action
TL;DR: The interplay between stem cells and their niche creates the dynamic system necessary for sustaining tissues, and for the ultimate design of stem-cell therapeutics.
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Cytokines in atherosclerosis: pathogenic and regulatory pathways.
Alain Tedgui,Ziad Mallat +1 more
TL;DR: Based on the current knowledge of the role of cytokines in atherosclerosis, some novel therapeutic strategies to combat this disease are proposed and the potential of circulating cytokine levels as biomarkers of coronary artery disease is discussed.
Journal ArticleDOI
Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment
TL;DR: A model is proposed in which antigen levels drive the hierarchical loss of different CD8 T-cell effector functions during chronic infection, leading to distinct stages of functional impairment and eventually to physical deletion of virus-specific T cells.
Journal ArticleDOI
CD4+CD25+ Immunoregulatory T Cells: Gene Expression Analysis Reveals a Functional Role for the Glucocorticoid-Induced TNF Receptor
Rebecca S. McHugh,Matthew J. Whitters,Ciriaco A. Piccirillo,Deborah A. Young,Ethan M. Shevach,Mary Collins,Michael C. Byrne +6 more
TL;DR: A number of genes that antagonize signaling, including members of the SOCS family, may contribute to their anergic phenotype and GITR abrogated suppression, demonstrating a functional role for this receptor in regulating the CD4(+)CD25(+) T cell subset.
References
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Journal ArticleDOI
Cytokines Induce the Development of Functionally Heterogeneous T Helper Cell Subsets
TL;DR: I would like to thank Bob Coffman, Thierry von der Weid, Nancy Hosken, Amy Beebe, Steve Hurst, and Douglas Robinson for useful suggestions and discussion and Lewis Lanier for critical reviewing of the mansucript.
Journal Article
Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells.
Steven E. Macatonia,Nancy Ann Hosken,Mark J. Litton,Pedro L. Vieira,Chyi-Song Hsieh,J. A. Culpepper,Maria Wysocka,Giorgio Trinchieri,Kenneth M. Murphy,Anne O'Garra +9 more
TL;DR: In addition to inducing proliferation and clonal expansion of naive T cells, dendritic cells, by their production of IL-12, play a direct role in the development of IFN-gamma-producing cells that are important for cell-mediated immune responses.
Journal ArticleDOI
Induction of th1 and th2 cd4+ t cell responses : the alternative approaches
TL;DR: The effects on Th priming of (a) using altered peptide ligands as antigens, (b) varying the dose of antigen, and (c) altering costimulatory signals are discussed.
Journal ArticleDOI
High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.
Franz Koch,Ursula Stanzl,P Jennewein,Katrin Janke,Christine Heufler,Eckhart Kämpgen,Nikolaus Romani,Gerold Schuler +7 more
TL;DR: Side-by-side comparison of IL-12 production, and blocking experiments employing an anti-CD40 ligand mAb, suggest that the CD40-mediated pathway is quantitatively more significant than induction via the MHC class II molecule.
Journal ArticleDOI
Receptor-Ligand Interaction Between CD44 and Osteopontin (Eta-1)
TL;DR: The cytokine osteopontin (Eta-1), which regulates similar cellular functions, was found to be a protein ligand of CD44, and may be exploited by tumor cells to promote metastasis formation.