Cd45rb Ligation Inhibits Allergic Pulmonary Inflammation by Inducing Ctla4 Transcription.
From: Department of Medicine, Pulmonary and Critical Medicine, School of Medicine, University of California, San Diego, CA 92093, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Sep 2007
- ISSN: 0022-1767
- Volume: 179
- Issue: 6
- Pages: 4212-8
- Medium: Print
- Language: English
- Citation (JAMA): Jen Kai Yu, Campo Monica, He Hongzhen, et al. Cd45rb Ligation Inhibits Allergic Pulmonary Inflammation by Inducing Ctla4 Transcription.. J. Immunol. Sep 2007;179:4212-8
Abstract
CD45, a type I transmembrane protein tyrosine phosphatase expressed on nucleated hemopoietic cells, is prominently involved in T cell activation. Ligation of CD45RB isoforms has been associated with transplant tolerance. A recent genotyping analysis of asthma indicates a correlation with CD45 splicing. In this study, we administered an anti-CD45RB mAb (aCD45) in a murine model of allergic asthma and found that CD45RB ligation decreases allergic responses. aCD45 decreases allergen-induced pulmonary eosinophilia, bronchoalveolar lavage IL-13, IgE, and airway responses. Also, aCD45 increases the expression of CTLA4, a negative regulator of T cell activation. Furthermore, CD45RB signals no longer decrease allergic inflammation when CTLA4 is inhibited. These data support a role for CTLA4 in CD45RB-mediated inhibition of allergic inflammation. T cells and splenocytes stimulated with aCD45 exhibited increased CTLA4 levels, and analysis of CTLA4 promoter gene constructs identified a CD45RB-inducible regulatory region localized from -335 to -62 bp relative to the transcription start site. Together, these findings suggest that CD45RB signals mediate a novel role in the modulation of allergic inflammation, orchestrated by T cells through induction of CTLA4 transcription.
Mesh Headings (Keywords): Animals, Antibodies, Monoclonal, Antigens, CD, Antigens, CD45, Antigens, Differentiation, Base Sequence, Cell Line, Cell Line, Tumor, Ligands, Lung, Male, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Ovalbumin, Promoter Regions (Genetics), Respiratory Hypersensitivity, Signal Transduction, Transcription, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 17785861
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