RANTES (CCL5) Regulates Airway Responsiveness after Repeated Allergen Challenge

Koya, Toshiyuki; Takeda, Katsuyuki; Kodama, Taku; Miyahara, Nobuaki; Matsubara, Shigeki; Balhorn, Annette; Joetham, Anthony; Dakhama, A.; Gelfand, Erwin W.

doi:10.1165/rcmb.2005-0394oc

Cited by 32 publications

(22 citation statements)

References 47 publications

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“…Consistent with the present report by Koya and colleagues, the history of CCL5 is closely linked to its actions in regulating T cell performance (3). Indeed, the initial naming of CCL5 (i.e., Regulated And Normal T cell Expressed and Secreted or RANTES) was based on T cell behavior.…”

Section: Non-t Cell Explanations: Ccl5 and The Macrophagesupporting

confidence: 89%

Chemokine Complexity

Grayson

Holtzman

2006

Am J Respir Cell Mol Biol

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Section: Non-t Cell Explanations: Ccl5 and The Macrophagesupporting

confidence: 89%

Chemokine Complexity

Grayson

Holtzman

2006

Am J Respir Cell Mol Biol

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“…The increased production of the Th1 cytokine IFN-␥ may have an additional protective effect by counterbalancing detrimental effects of Th2 cytokines (55,56). The chemokine RANTES is important in controlling eosinophil migration (57) and airway hyperresponsiveness in an ovalbuminsensitized murine model (58), and the reduced RANTES expression in the lungs of eotaxin-and/or IL-5-deficient cohorts may contribute to protection from pathology in these mice. Another chemokine, TARC, has recently been reported to be highly increased in acute RSV infection (41).…”

Section: Discussionmentioning

confidence: 99%

Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease

Townsend

Herrero

et al. 2015

J Virol

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Human respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood. In vivo studies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin-and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin-and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load. IMPORTANCEThis study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity. R espiratory syncytial virus (RSV) is a serious lower respiratory tract infection in infants, the elderly, and the immunocompromised (1-4), resulting in Ͼ130,000 hospitalizations in the United States each year (5, 6). Children who experience acute RSV infection of the lower respiratory tract have an increased likelihood of developing childhood asthma (7). To date, there is no safe and effective RSV vaccine available. This is in part linked to the negative outcome of a 1960s clinical trial using a formalin-inactivated alum-precipitated RSV (FI-RSV) vaccine (8). Children immunized with the FI-RSV vaccine experienced more severe disease following subsequent natural exposure to RSV, with one study showing 69% of immunized children developing pneumonia compared to only 9% of children in the unimmunized control group (9). In a second study, 80% of FI-RSV-immunized infants were hospitalized and two died, compared with only 5% hospitalization and no death in the control group (10). FI-RSV vaccineenhanced illness was clinically characterized as severe primary RSV infection, with bronchiolitis, hypoxemia, and pneumonia. However, in contrast to the neutrophilic inflammation observed during primary RSV infection, the more severe a...

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“…In animals infected with respiratory syncytial virus, anti-RANTES suppressed the development of AHR (24). However, after repeated allergen challenge, anti-RANTES enhanced AHR (25). Therefore, the role of RANTES appears to be complex, and might depend on the phase of allergic responses when interference is introduced.…”

Section: Sensitized T Cells Obtained From Ccr5mentioning

confidence: 99%

Requirement for Chemokine Receptor 5 in the Development of Allergen-Induced Airway Hyperresponsiveness and Inflammation

Fuchimoto

Kanehiro

Miyahara

et al. 2011

Am J Respir Cell Mol Biol

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Chemokine receptor (CCR) 5 is expressed on dendritic cells, macrophages, CD8 cells, memory CD4 T cells, and stromal cells, and is frequently used as a marker of T helper type 1 cells. Interventions that abrogate CCR5 or interfere with its ligand binding have been shown to alter T helper type 2-induced inflammatory responses. The role of CCR5 on allergic airway responses is not defined. CCR5-deficient (CCR5 2/2 ) and wild-type (CCR5 1/1 ) mice were sensitized and challenged with ovalbumin (OVA) and allergic airway responses were monitored 48 hours after the last OVA challenge. Cytokine levels in lung cell culture supernatants were also assessed. CCR5 2/2 mice showed significantly lower airway hyperresponsiveness (AHR) and lower numbers of total cells, eosinophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid compared with CCR51/1 mice after sensitization and challenge. The levels of IL-4 and IL-13 in BAL fluid of CCR5 2/2 mice were lower than in CCR5 1/1 mice. Decreased numbers of lung T cells were also detected in CCR52/2 mice after sensitization and challenge. Transfer of OVAsensitized T cells from CCR5 1/1 , but not transfer of CCR5 2/2 cells, into CCR52/2 mice restored AHR and numbers of eosinophils in BAL fluid after OVA challenge. Accordingly, the numbers of airwayinfiltrating donor T cells were significantly higher in the recipients of CCR5 1/1 T cells. Taken together, these data suggest that CCR5 plays a pivotal role in allergen-induced AHR and airway inflammation, and that CCR5 expression on T cells is essential to the accumulation of these cells in the airways.

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RANTES (CCL5) Regulates Airway Responsiveness after Repeated Allergen Challenge

Cited by 32 publications

References 47 publications

Chemokine Complexity

Chemokine Complexity

Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease

Requirement for Chemokine Receptor 5 in the Development of Allergen-Induced Airway Hyperresponsiveness and Inflammation

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