Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity.
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-gamma 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.
Ashkar
S
S
Laboratory for Skeletal Disorders and Rehabilitation, Department of Orthopedic Surgery, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Weber
G F
GF
Panoutsakopoulou
V
V
Sanchirico
M E
ME
Jansson
M
M
Zawaideh
S
S
Rittling
S R
SR
Denhardt
D T
DT
Glimcher
M J
MJ
Cantor
H
H
D000818:Animals; D006099:Granuloma / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D016849:Keratitis, Herpetic / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053495:Osteopontin; D010766:Phosphorylation; D019030:Receptors, Vitronectin / Q000378:metabolism; D012795:Sialoglycoproteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D018960:Hyaluronan Receptors; D019030:Receptors, Vitronectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma