Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation.

Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. Research Abstract Details 

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Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. Abstract Text:

Jeanette P Brown,Christian Taube,Nobuaki Miyahara,Toshiyuki Koya,Roberta Pelanda,Erwin W Gelfand,Raul M Torres,

RATIONALE: Arhgef1 is an intracellular protein, expressed by hematopoietic cells, that regulates signaling by both G protein-coupled receptors and RhoA, and, consequently, is required for appropriate migration and adhesion of diverse leukocyte populations. OBJECTIVES: To evaluate a possible contribution for Arhgef1 in the development of airway inflammation and airway hyperreactivity. Methods: Arhgef1-deficient (Arhgef1-/-) and wild-type (WT) mice were sensitized and airway challenged, followed by measurement of airway responsiveness to inhaled methacholine. Inflammation was assessed by several parameters that included flow cytometric analysis and histology. Arhgef1-deficient recipients were reconstituted with WT T lymphocytes before sensitization and challenge, and again measured for airway responsiveness and inflammation. Cytokine production in response to specific antigen was measured in cultures of isolated leukocytes from lung and spleen and compared with the levels generated in lung and spleen explant cultures. MEASUREMENTS AND MAIN RESULTS: Arhgef1-/- mice display significantly reduced airway hyperreactivity, Th2 cytokine production, and lung inflammation, despite intact systemic immunity. After airway challenge of Arhgef1-/- mice, antigen-specific T cells were present in mutant lungs, but were found to interact with CD11c+ cells at a significantly reduced frequency. Adoptive transfer of WT T cells into Arhgef1-/- mice restored airway hyperreactivity and inflammation. CONCLUSIONS: These data demonstrate that T cells depend on Arhgef1 to promote lung inflammation. Moreover, a deficiency in Arhgef1 results in reduced T cell-CD11c+ antigen-presenting cell interaction, and likely underscores the inability of Arhgef1-/- mice to mount an adaptive immune response to airway challenge.

Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. Publishing Authors By Initials

JP Brown,C Taube,N Miyahara,T Koya,R Pelanda,EW Gelfand,RM Torres,

For similar cells: blood cells: leukocytes: leukocytes, mononuclear: lymphocytes: t-lymphocytes: cd4-positive t-lymphocytes: t-lymphocytes, helper-inducer: th2 cells research abstracts see: cells: blood cells: leukocytes: leukocytes, mononuclear: lymphocytes: t-lymphocytes: cd4-positive t-lymphocytes: t-lymphocytes, helper-inducer: th2 cells research

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Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: American journal of respiratory and critical care

VOLUME: 176

Page Numbers: 10-9

Journal Abbreviation: Am. J. Respir. Crit. Care Med.

ISSN: 1535-4970

DAY: 26

MONTH: 04

YEAR: 2007

Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9421642

Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. Keywords Mesh Terms:

KEYWORDS: Th2 Cells

MESH TERMS: immunology

Chemical & Substance for Abstract: Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. Information

Substance Name: Proto-Oncogene Proteins

Registry Number: 0

Grant and Affiliation Information for Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation.

AFFILIATION: Integrated Department of Immunology, University of Colorado at Denver and Health Sciences Center and National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL-61005

ACRONYM: HL

MEDLINETA: Am J Respir Crit Care Med

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