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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/238849
- author
- Forssell, J
; Sideras, Paschalis
LU
; Eriksson, C
; Malm-Erjefält, Monika
LU
; Rydell-Törmänen, Kristina
LU
; Ericsson, PO
and Erjefält, Jonas
LU
- organization
- publishing date
- 2005
- 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
- pmid:15778496
- 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
- 2016-04-01 12:27:37
- date last changed
- 2022-01-27 05:21:07
@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}},
keywords = {{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}},
doi = {{10.1165/rcmb.2004-0348OC}},
volume = {{32}},
year = {{2005}},
}