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Interleukin-2-inducible T cell kinase regulates mast cell degranulation and acute allergic responses

Forssell, J; Sideras, Paschalis LU ; Eriksson, C; Malm-Erjefält, Monika LU ; Rydell-Törmänen, Kristina LU ; Ericsson, PO and Erjefält, Jonas LU (2005) In American Journal of Respiratory Cell and Molecular Biology 32(6). p.511-520
Abstract
Bruton's tyrosine kinase (Btk) is thought to positively regulate mast cell activation, implying a role in allergic responses. We have compared acute and late phase allergic airway reactions in mice lacking either Btk or interleukin-2-inducible T cell kinase (Itk), another Tec kinase expressed in mast cells. Btk(-/-) mice showed minor protection against allergic symptoms when challenged with allergen via the airways. In sharp contrast, both acute and late phase inflammatory allergic responses were markedly reduced in Itk(-/-) mice. Notably, airway mast cell degranulation in Itk(-/-) mice was severely impaired, despite wild-type levels of allergen-specific IgE and IgG(1). The degranulation defect was confirmed in DNP-conjugated human serum... (More)
Bruton's tyrosine kinase (Btk) is thought to positively regulate mast cell activation, implying a role in allergic responses. We have compared acute and late phase allergic airway reactions in mice lacking either Btk or interleukin-2-inducible T cell kinase (Itk), another Tec kinase expressed in mast cells. Btk(-/-) mice showed minor protection against allergic symptoms when challenged with allergen via the airways. In sharp contrast, both acute and late phase inflammatory allergic responses were markedly reduced in Itk(-/-) mice. Notably, airway mast cell degranulation in Itk(-/-) mice was severely impaired, despite wild-type levels of allergen-specific IgE and IgG(1). The degranulation defect was confirmed in DNP-conjugated human serum albumin-challenged mice passively sensitized with anti-DNP IgE antibodies, and was also observed after direct G-protein stimulation with the mast cell secretagogue c48/80. Moreover, late phase inflammatory changes, including eosinophilia, lymphocyte infiltration, and Th-2 cytokine production in the lungs, was eliminated in Itk(-/-) mice. Collectively, our data suggest a critical role of Itk in airway mast cell degranulation in vivo that together with an impaired T cell response prevents the development of both acute and late phase inflammatory allergic reactions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
allergy and immunology, asthma, signal transduction
in
American Journal of Respiratory Cell and Molecular Biology
volume
32
issue
6
pages
511 - 520
publisher
American Thoracic Society
external identifiers
  • pmid:15778496
  • wos:000229518700006
  • scopus:20044390229
ISSN
1535-4989
DOI
10.1165/rcmb.2004-0348OC
language
English
LU publication?
yes
id
a4a59bf0-9dee-4b54-89ab-1aba3132b7ce (old id 238849)
date added to LUP
2007-08-15 09:56:08
date last changed
2017-01-01 05:09:43
@article{a4a59bf0-9dee-4b54-89ab-1aba3132b7ce,
  abstract     = {Bruton's tyrosine kinase (Btk) is thought to positively regulate mast cell activation, implying a role in allergic responses. We have compared acute and late phase allergic airway reactions in mice lacking either Btk or interleukin-2-inducible T cell kinase (Itk), another Tec kinase expressed in mast cells. Btk(-/-) mice showed minor protection against allergic symptoms when challenged with allergen via the airways. In sharp contrast, both acute and late phase inflammatory allergic responses were markedly reduced in Itk(-/-) mice. Notably, airway mast cell degranulation in Itk(-/-) mice was severely impaired, despite wild-type levels of allergen-specific IgE and IgG(1). The degranulation defect was confirmed in DNP-conjugated human serum albumin-challenged mice passively sensitized with anti-DNP IgE antibodies, and was also observed after direct G-protein stimulation with the mast cell secretagogue c48/80. Moreover, late phase inflammatory changes, including eosinophilia, lymphocyte infiltration, and Th-2 cytokine production in the lungs, was eliminated in Itk(-/-) mice. Collectively, our data suggest a critical role of Itk in airway mast cell degranulation in vivo that together with an impaired T cell response prevents the development of both acute and late phase inflammatory allergic reactions.},
  author       = {Forssell, J and Sideras, Paschalis and Eriksson, C and Malm-Erjefält, Monika and Rydell-Törmänen, Kristina and Ericsson, PO and Erjefält, Jonas},
  issn         = {1535-4989},
  keyword      = {allergy and immunology,asthma,signal transduction},
  language     = {eng},
  number       = {6},
  pages        = {511--520},
  publisher    = {American Thoracic Society},
  series       = {American Journal of Respiratory Cell and Molecular Biology},
  title        = {Interleukin-2-inducible T cell kinase regulates mast cell degranulation and acute allergic responses},
  url          = {http://dx.doi.org/10.1165/rcmb.2004-0348OC},
  volume       = {32},
  year         = {2005},
}