title: The role of protein tyrosine phosphatases in the regulation of allergic asthma: implication of TC-PTP and PTP-1B in the modulation of disease development.
abstract: Protein tyrosine phosphorylation is an important early event in the signal transduction of numerous cell receptors involved in the immune response. The implication of protein tyrosine kinases in allergic asthma is well recognized, but the role of protein tyrosine phosphatases (PTPs) remains poorly understood. However, we recently reported that global inhibition of PTPs during either the allergen-sensitization phase or the allergen-challenge phase reduced the development of asthma and that this correlated with an increased T helper 1 (Th1) response in both lung and spleen tissues. Therefore, in this study we investigated individual roles of PTPs involved in regulating the immune response. We observed that genetic deficiency for PTP-1B resulted in increased recruitment of lung inflammatory cells, while protein tyrosine phosphatase-phosphatase and tensin homologue deleted (PTP-PEST)-deficient mice exhibited a phenotype similar to that of wild-type mice. Importantly, we found that a heterozygous mutation of T cell PTP (TC-PTP) dramatically abrogates immunoglobulin E production and reduces the recruitment of inflammatory cells to the lung, conferring an important role for TC-PTP in the development of allergic asthma. As opposed to other studies on Src homology phosphatase-1 (SHP-1) deficiency, specific acute SHP-1 inhibition during allergen challenge did not affect disease outcome. Collectively, our results underscore the importance of PTPs in the development of allergic asthma.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, QC.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pouliot
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bergeron
authors.forename: André
authors.initials: A
authors.lastname: Marette
authors.forename: Martin
authors.initials: M
authors.lastname: Olivier
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D015153:Blotting, Western / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000276:immunology; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics / Q000276:immunology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000485:Allergens; D007073:Immunoglobulin E; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse; C516653:Ptpn2 protein, mouse; C509248:Ptpn6 protein, mouse