Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma

Center for Molecular Immunology and Infectious Disease and Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Journal of Experimental Medicine (Impact Factor: 13.91). 07/2008; 205(6):1285-92. DOI: 10.1084/jem.20071836
Source: PubMed

ABSTRACT Eosinophils have been implicated as playing a major role in allergic airway responses. However, the importance of these cells to the development of this disease has remained ambiguous despite many studies, partly because of lack of appropriate model systems. In this study, using transgenic murine models, we more clearly delineate a role for eosinophils in asthma. We report that, in contrast to results obtained on a BALB/c background, eosinophil-deficient C57BL/6 Delta dblGATA mice (eosinophil-null mice via the Delta DblGATA1 mutation) have reduced airway hyperresponsiveness, and cytokine production of interleukin (IL)-4, -5, and -13 in ovalbumin-induced allergic airway inflammation. This was caused by reduced T cell recruitment into the lung, as these mouse lungs had reduced expression of CCL7/MCP-3, CC11/eotaxin-1, and CCL24/eotaxin-2. Transferring eosinophils into these eosinophil-deficient mice and, more importantly, delivery of CCL11/eotaxin-1 into the lung during the development of this disease rescued lung T cell infiltration and airway inflammation when delivered together with allergen. These studies indicate that on the C57BL/6 background, eosinophils are integral to the development of airway allergic responses by modulating chemokine and/or cytokine production in the lung, leading to T cell recruitment.

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Available from: Alison Humbles, May 29, 2015
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    • "Asthmatic endothelial P­selectin can also directly activate eosinophil at­ tachment to the endothelium (Johansson and Mosher, 2011). Eosinophils are required for and can significantly augment the severity of the allergen­induced inflammation by secret­ ing Th2 cytokines (Rosenberg et al., 2007), activating and re­ cruiting T cells (MacKenzie et al., 2001; Mattes et al., 2002; Jacobsen et al., 2008; Walsh et al., 2008), and modulating den­ dritic cell responses (Jacobsen et al., 2008). Additional studies will be required to further define the mechanisms that the VEGF–miR­1–Mpl–P­selectin pathway uses to regulate pul­ monary Th2 responses. "
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    Journal of Experimental Medicine 09/2013; 210(10). DOI:10.1084/jem.20121200 · 13.91 Impact Factor
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    • "In wild-type mice, allergen-induced airway inflammation is characterized by a Th2 immune bias that is diminished in association with impaired eosinophil recruitment in CCR3-deficient, CCL11/CCL24 double-deficient and IL-5/CCL11 double-deficient mice (Fulkerson et al. 2006a; Mattes et al. 2002), and in two distinct strains of mice on the C57BL/6 background genetically engineered to be devoid of eosinophils (Jacobsen et al. 2008; Lee et al. 2004; Walsh et al. 2008). In the latter cases, a defect in Th2 effector cell recruitment was also observed that was restored upon adoptive transfer of eosinophils (Jacobsen et al. 2008; Walsh et al. 2008). Of note, in contrast to their C57BL/6 counterparts, eosinophil-deficient ΔdblGATA1−/− mice on the BALB/c background exhibited no obvious defects in Th2 cell induction in response to airway allergen challenge (Humbles et al. 2004). "
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    • "Mouse strain specific differences in airway hyperreac - tivity and Th2 responses have been noted in models of acute asthma ( Tumes et al . 2007 ; Walsh et al . 2008 ; Zhu and Gilmour 2009 ) and models of airway remodeling ( Hirota et al . 2009 ; Shinagawa and Kojima 2003 ; Van Hove et al . 2009"
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