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Tim1 and Tim3 are not essential for experimental allergic asthma
BACKGROUND: Initial studies suggested that polymorphisms in Tim1 and Tim3 contribute to the development of airway hyperreactivity (AHR) in an acute mouse model of asthma. This was also mirrored in human genetic studies where polymorphisms in Tim1 and Tim3 have been associated with atopic populations...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132443/ https://www.ncbi.nlm.nih.gov/pubmed/21470319 http://dx.doi.org/10.1111/j.1365-2222.2011.03728.x |
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author | Barlow, J L Wong, S H Ballantyne, S J Jolin, H E McKenzie, A N J |
author_facet | Barlow, J L Wong, S H Ballantyne, S J Jolin, H E McKenzie, A N J |
author_sort | Barlow, J L |
collection | PubMed |
description | BACKGROUND: Initial studies suggested that polymorphisms in Tim1 and Tim3 contribute to the development of airway hyperreactivity (AHR) in an acute mouse model of asthma. This was also mirrored in human genetic studies where polymorphisms in Tim1 and Tim3 have been associated with atopic populations. OBJECTIVE: Further studies using anti-Tim1 or -Tim3 antibodies, or Tim fusion proteins, have also suggested that these molecules may function as regulators of type-1 and type-2 immunity. However, their role in the development of AHR and airway inflammation remains unclear. Given the proposed roles for Tim1 and Tim3 in type-1 and type-2 responses, we sought to determine whether these molecules were important in regulating antigen-driven lung allergy and inflammation. METHOD: We used Tim1- and Tim3-deficient mice and determined how the development of allergic lung inflammation was affected. RESULTS: AHR was induced normally in the absence of both Tim1 and Tim3, although Tim1-deficient mice did show a small but significant decrease in cell infiltration in the lung and blood eosinophilia. Although Tim3 was expressed on CD4(+) T cells in the allergic lung, Tim1 expression was restricted to CD86(+) B cells. CONCLUSIONS AND CLINICAL RELEVANCE: Thus, Tim1 and Tim3 are not essential for the induction of the type-2 response in lung allergy. This is contrary to what was proposed in a number of other studies using neutralizing and activating antibodies and questions the clinical relevance of Tim1 and Tim3 for novel allergy therapies. Cite this as: J. L. Barlow, S. H. Wong, S. J. Ballantyne, H. E. Jolin and A. N. J. McKenzie, Clinical & Experimental Allergy, 2011 (41) 1012–1021. |
format | Online Article Text |
id | pubmed-3132443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-31324432011-07-11 Tim1 and Tim3 are not essential for experimental allergic asthma Barlow, J L Wong, S H Ballantyne, S J Jolin, H E McKenzie, A N J Clin Exp Allergy Original Articles: Experimental Models of Allergic Disease BACKGROUND: Initial studies suggested that polymorphisms in Tim1 and Tim3 contribute to the development of airway hyperreactivity (AHR) in an acute mouse model of asthma. This was also mirrored in human genetic studies where polymorphisms in Tim1 and Tim3 have been associated with atopic populations. OBJECTIVE: Further studies using anti-Tim1 or -Tim3 antibodies, or Tim fusion proteins, have also suggested that these molecules may function as regulators of type-1 and type-2 immunity. However, their role in the development of AHR and airway inflammation remains unclear. Given the proposed roles for Tim1 and Tim3 in type-1 and type-2 responses, we sought to determine whether these molecules were important in regulating antigen-driven lung allergy and inflammation. METHOD: We used Tim1- and Tim3-deficient mice and determined how the development of allergic lung inflammation was affected. RESULTS: AHR was induced normally in the absence of both Tim1 and Tim3, although Tim1-deficient mice did show a small but significant decrease in cell infiltration in the lung and blood eosinophilia. Although Tim3 was expressed on CD4(+) T cells in the allergic lung, Tim1 expression was restricted to CD86(+) B cells. CONCLUSIONS AND CLINICAL RELEVANCE: Thus, Tim1 and Tim3 are not essential for the induction of the type-2 response in lung allergy. This is contrary to what was proposed in a number of other studies using neutralizing and activating antibodies and questions the clinical relevance of Tim1 and Tim3 for novel allergy therapies. Cite this as: J. L. Barlow, S. H. Wong, S. J. Ballantyne, H. E. Jolin and A. N. J. McKenzie, Clinical & Experimental Allergy, 2011 (41) 1012–1021. Blackwell Publishing Ltd 2011-07 /pmc/articles/PMC3132443/ /pubmed/21470319 http://dx.doi.org/10.1111/j.1365-2222.2011.03728.x Text en Copyright © 2011 Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Original Articles: Experimental Models of Allergic Disease Barlow, J L Wong, S H Ballantyne, S J Jolin, H E McKenzie, A N J Tim1 and Tim3 are not essential for experimental allergic asthma |
title | Tim1 and Tim3 are not essential for experimental allergic asthma |
title_full | Tim1 and Tim3 are not essential for experimental allergic asthma |
title_fullStr | Tim1 and Tim3 are not essential for experimental allergic asthma |
title_full_unstemmed | Tim1 and Tim3 are not essential for experimental allergic asthma |
title_short | Tim1 and Tim3 are not essential for experimental allergic asthma |
title_sort | tim1 and tim3 are not essential for experimental allergic asthma |
topic | Original Articles: Experimental Models of Allergic Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132443/ https://www.ncbi.nlm.nih.gov/pubmed/21470319 http://dx.doi.org/10.1111/j.1365-2222.2011.03728.x |
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