Document Detail

Regulation of pulmonary fibrosis by chemokine receptor CXCR3.
MedLine Citation:
PMID:  15254596     Owner:  NLM     Status:  MEDLINE    
CXC chemokine receptor 3 (CXCR3) is the receptor for the IFN-gamma-inducible C-X-C chemokines MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11. CXCR3 is expressed on activated immune cells and proliferating endothelial cells. The role of CXCR3 in fibroproliferation has not been investigated. We examined the role of CXCR3 in pulmonary injury and repair in vivo. CXCR3-deficient mice demonstrated increased mortality with progressive interstitial fibrosis relative to WT mice. Increased fibrosis occurred without increased inflammatory cell recruitment. CXCR3 deficiency resulted in both a reduced early burst of IFN-gamma production and decreased expression of CXCL10 after lung injury. We identified a relative deficiency in lung NK cells in the unchallenged CXCR3-deficient lung and demonstrated production of IFN-gamma by WT lung NK cells in vivo following lung injury. The fibrotic phenotype in the CXCR3-deficient mice was significantly reversed following administration of exogenous IFN-gamma or restoration of endogenous IFN-gamma production by adoptive transfer of WT lymph node and spleen cells. Finally, pretreatment of WT mice with IFN-gamma-neutralizing Ab's enhanced fibrosis following lung injury. These data demonstrate a nonredundant role for CXCR3 in limiting tissue fibroproliferation and suggest that this effect may be mediated, in part, by the innate production of IFN-gamma following lung injury.
Dianhua Jiang; Jiurong Liang; Jennifer Hodge; Bao Lu; Zhou Zhu; Shuang Yu; Juan Fan; Yunfei Gao; Zhinan Yin; Robert Homer; Craig Gerard; Paul W Noble
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  114     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-15     Completed Date:  2004-08-31     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  291-9     Citation Subset:  AIM; IM    
Department of Medicine, Section of Pulmonary and Critical Care, Yale University School of Medicine, New Haven, Connecticut 06520-8057, USA.
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MeSH Terms
Adoptive Transfer
Antibiotics, Antineoplastic / toxicity
Bleomycin / toxicity
Bronchoalveolar Lavage
Interferon-gamma / administration & dosage,  metabolism*
Killer Cells, Natural / immunology,  metabolism
Lymph Nodes / cytology
Lymphocytes / metabolism
Mice, Inbred C57BL
Mice, Knockout
Pulmonary Fibrosis / chemically induced,  immunology,  metabolism*,  pathology
Receptors, CXCR3
Receptors, Chemokine / genetics,  metabolism*
Spleen / cytology
Grant Support
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Cxcr3 protein, mouse; 0/Receptors, CXCR3; 0/Receptors, Chemokine; 11056-06-7/Bleomycin; 82115-62-6/Interferon-gamma
Comment In:
J Clin Invest. 2004 Jul;114(2):165-8   [PMID:  15254582 ]

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