Coordinated Involvement of Mast Cells and T Cells in Allergic Mucosal Inflammation: Critical Role of the CC Chemokine Ligand 1:CCR8 Axis

Gonzalo, José-Ángel; Qiu, Yubin; Lora, José M.; Al-Garawi, Amal; Villeval, Jean‐Luc; Boyce, Joshua A.; Martı́nez-A, Carlos; Márquez, Gabriel; Goya, Innigo; Hamid, Qutayba; Fraser, Christopher C.; Picarella, Dominic; Cote-Sierra, Javier; Hodge, Martin R.; Gutierrez-Ramos, José-Carlos; Kolbeck, Roland; Coyle, Anthony J.

doi:10.4049/jimmunol.179.3.1740

Cited by 65 publications

(64 citation statements)

References 52 publications

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“…In addition, the number of CD4+ lymphocytes or mast cells did not contribute independently to improvement of BHR. Thus, in contrast to asthma, our findings do not suggest a large contribution of CD4+ lymphocytes or mast cells to the severity of BHR in COPD, but rather highlight the contribution of sputum neutrophils, lymphocytes and macrophages [32,33].…”

Section: Discussionmentioning

confidence: 65%

Clinical and inflammatory determinants of bronchial hyperresponsiveness in COPD

Berge

Vonk

Gosman³

et al. 2012

Eur Respir J

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Bronchial hyperresponsiveness (BHR) is regarded as a hallmark of asthma, yet it is also present in a considerable number of chronic obstructive pulmonary disease (COPD) patients. Epidemiological studies have shown that BHR provides complementary information to forced expiratory volume in 1 s (FEV1) for development and progression of COPD. We hypothesised that the severity of BHR and its longitudinal changes associate with both clinical and airway inflammation measures in COPD.Our hypothesis was tested in 114 COPD patients (median age 62.9 years, smoking exposure 45.9 pack-yrs) participating in the GLUCOLD (Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease) study, which previously showed an improvement in BHR with fluticasone and fluticasone/salmeterol. At baseline, and 6 and 30 months after treatment, we investigated lung function, including body plethysmography, provocative concentration of methacholine causing a 20% fall in FEV1, sputum induction, and bronchial biopsies.By performing both cross-sectional and longitudinal analyses, we show that BHR in COPD is predominantly associated with residual volume/total lung capacity (a measure of air trapping) and airway inflammation reflected by the number of neutrophils, macrophages and lymphocytes in sputum and bronchial biopsies.Our findings indicate that BHR is an independent trait in COPD and provides important information on phenotype heterogeneity and disease activity.

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Section: Discussionmentioning

confidence: 65%

Clinical and inflammatory determinants of bronchial hyperresponsiveness in COPD

Berge

Vonk

Gosman³

et al. 2012

Eur Respir J

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“…Our results further support a role for these other cell types contributing to the total levels of Th2 cytokines in the lung, yet not to the level attainable when CD4 + T cells also contribute. Mast cells are an abundant source of CCL1 following FcεRI-mediated activation and are critically important in the chemotactic recruitment of CCR8-expressing CD4 + T cells (25,38), a relationship central in the development of asthmatic mucosal inflammation in the lung (7). We have detected a deficiency of CCL1 in the lungs of asthmatic mice with Egr2-deficient mast cells (Fig.…”

Section: Discussionmentioning

confidence: 70%

“…Mast cells can direct the migration of CD4 + CD25 + T regulatory cells through the CCL1-CCR8 axis (7,25). To investigate the role of Egr2-dependent mast cell CCL1 in T cell migration, an in vitro Transwell migration assay was conducted.…”

Section: Egr2-dependent Mast Cell Ccl1 Production Drives Cd4 + T Cellmentioning

confidence: 99%

“…In the lung mucosa, local mast cells activated through IgE have been shown to be critical in mediating the recruitment of CD4 + T cells and directing the subsequent allergic inflammatory pathology (7). Communication between locally activated mast cells and peripheral CD4 + T cells is regulated through mast cell-produced CCL1 and its receptor, CCR8, expressed on the surface of CD4 + T cells, an interaction termed the CCL1-CCR8 axis (8).…”

mentioning

confidence: 99%

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Mast Cell FcεRI-Induced Early Growth Response 2 Regulates CC Chemokine Ligand 1–Dependent CD4+ T Cell Migration

MacNeil

Junkins

et al. 2013

The Journal of Immunology

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Mast cells are well positioned in host tissue for detecting environmental signals, including allergens, leading to activation of the high-affinity IgE receptor FcεRI, and initiating a signaling cascade that perpetuates the production of biologically potent mediators, including chemokines. We have identified a novel target of mast cell FcεRI activity in the transcription factor early growth response 2 (Egr2) and sought to characterize its function therein. Egr2 was transiently activated following FcεRI-mediated signaling, targeted the promoter of the chemokine CCL1, and was critical for allergen-induced mast cell CCL1 production. Egr2-deficient mast cells were incapable of directing CD4+ T cell migration via the CCL1–CCR8 axis. In a model of allergic asthma, reconstitution of mast cell–deficient mice with Egr2-deficient mast cells demonstrated that mast cell Egr2 was essential for migration of CD4+ T cells to the inflamed lung. These findings position Egr2 as a critical regulator of mast cell–directed CD4+ T cell migration.

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“…Chemokines are a class of small molecules, which promote leukocyte migration toward themselves [12]. CCL-1 is among the first discovered CC class of chemokines, which are mainly secreted by activated T cells, mast cells and macrophages [13][14][15][16][17]. Recently, it has been shown that autocrine CCL-1 produced from leukocellular lymphoma and adult cell leukemia has an anti-apoptotic effect [18].…”

Section: Discussionmentioning

confidence: 99%