Publication Date:
2000-02-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ashkar, S -- Weber, G F -- Panoutsakopoulou, V -- Sanchirico, M E -- Jansson, M -- Zawaideh, S -- Rittling, S R -- Denhardt, D T -- Glimcher, M J -- Cantor, H -- AI12184/AI/NIAID NIH HHS/ -- AI37833/AI/NIAID NIH HHS/ -- CA76176/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Feb 4;287(5454):860-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Skeletal Disorders and Rehabilitation, Department of Orthopedic Surgery, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10657301" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD44/metabolism
;
Granuloma/immunology
;
Herpes Simplex/immunology
;
Herpesvirus 1, Human/immunology
;
Hypersensitivity, Delayed
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Interferon-gamma/biosynthesis
;
Interleukin-10/*biosynthesis
;
Interleukin-12/*biosynthesis
;
Keratitis, Herpetic/immunology
;
Listeriosis/immunology
;
Lymphocyte Activation
;
Macrophages/*immunology
;
Mice
;
Mice, Inbred C3H
;
Mice, Inbred C57BL
;
Mice, Nude
;
Osteopontin
;
Phosphorylation
;
Receptors, Vitronectin/metabolism
;
Sialoglycoproteins/*immunology/metabolism/pharmacology
;
T-Lymphocytes/*immunology/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
