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http://purl.uniprot.org/citations/19541353http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19541353http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19541353http://www.w3.org/2000/01/rdf-schema#comment"

Background

T(H)1 cell-mediated immunity is essential for host defense against a variety of intracellular pathogens, such as mycobacteria, salmonella, and Leishmania species. A major T(H)1-mediated effector mechanism involves the IFN-gamma-induced killing of the pathogen by infected macrophages.

Objectives

The range of known T(H)1-specific effector molecules is limited, especially in human subjects. We sought to identify novel effector molecules that might be involved in T(H)1-mediated pathogen clearance.

Methods

We performed microarray-based analysis of human T(H)1 and T(H)2 cells to identify T(H)1-specific molecules. These analyses identified the extracellular matrix molecule fibronectin as a highly expressed T(H)1-specific molecule. We examined the expression of fibronectin in a variety of human cell types by using real-time RT-PCR, ELISA, and Western blotting. We also studied the role of fibronectin in modulating monocyte phenotype using in vitro culture.

Results

We show that human T(H)1 cells constitutively express and secrete fibronectin after in vitro differentiation from naive precursors. Furthermore, we demonstrate that ex vivo human T(H)1 cells selectively express fibronectin when compared with T(H)2 cells. The predominant isoform of fibronectin expressed by T(H)1 cells contains additional domains of the protein responsible for alpha4beta1 integrin binding and activation of Toll-like receptor 4. We show that treatment of monocytes with T(H)1 cell-derived fibronectin induces expression of the proinflammatory cytokine IL-6 while inhibiting IL-10 expression.

Conclusions

Because fibronectin also plays a major role in the attachment and opsonization of numerous intracellular pathogens, we propose that it might be a critical molecule produced by T(H)1 cells involved in pathogen eradication."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2009.04.036"xsd:string
http://purl.uniprot.org/citations/19541353http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2009.04.036"xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Lee T.H."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Lee T.H."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Cousins D.J."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Cousins D.J."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"McDonald J."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"McDonald J."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Gilmour J."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Gilmour J."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Sandig H."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Sandig H."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Arno M."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/author"Arno M."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/name"J. Allergy Clin. Immunol."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/name"J Allergy Clin Immunol"xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/pages"528-535"xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/pages"528-535"xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/title"Fibronectin is a TH1-specific molecule in human subjects."xsd:string
http://purl.uniprot.org/citations/19541353http://purl.uniprot.org/core/title"Fibronectin is a TH1-specific molecule in human subjects."xsd:string