IL-13 induces eosinophil recruitment into the lung by an IL-5– and eotaxin-dependent mechanism

Pope, Samuel M.; Brandt, Eric B.; Mishra, Anil; Hogan, Simon P.; Zimmermann, Nives; Matthaei, Klaus I.; Foster, Paul S.; Rothenberg, Marc E.

doi:10.1067/mai.2001.118600

Cited by 263 publications

(193 citation statements)

References 55 publications

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“…Third, we have established that IL-13-induced lung eosinophilia is differentially regulated by eotaxin-2 compared with eotaxin-1. In particular, our prior studies have shown that eotaxin-1 is required for the development of peribronchial eosinophilia (39). Our current study, demonstrating that eotaxin-2 is critical for the development of eosinophilia in the airway lumen (in response to IL-13), provides an integrated mechanism to explain the nonredundant roles for these two selective CCR3 ligands.…”

Section: Discussionmentioning

confidence: 78%

“…By using experimental models of antigen-induced airway inflammation, eotaxin-1 has been demonstrated to partially regulate eosinophil recruitment during the late phase response following repetitive mucosal antigen challenges (37,38). Mice deficient in both eotaxin-1 and IL-5 have a synergistic deficiency of lung eosinophils compared with mice deficient in either cytokine alone (39). Also, eotaxin-1/IL-5 double-deficient mice have an intrinsic deficiency in IL-13 production by antigen-specific CD4 ϩ cells, demonstrating that eosinophils, eotaxin-1, and IL-13 cooperate in allergic airway inflammation (40).…”

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confidence: 95%

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Identification of a Cooperative Mechanism Involving Interleukin-13 and Eotaxin-2 in Experimental Allergic Lung Inflammation

Pope

Fulkerson

Blanchard

et al. 2005

Journal of Biological Chemistry

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139

124

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Pulmonary eosinophilia, a hallmark pathologic feature of allergic lung disease, is regulated by interleukin-13 (IL-13) as well as the eotaxin chemokines, but the specific role of these cytokines and their cooperative interaction are only partially understood. First, we elucidated the essential role of IL-13 in the induction of the eotaxins by comparing IL-13 gene-targeted mice with wild type control mice by using an ovalbumin-induced model of allergic airway inflammation. Notably, ovalbumin-induced expressions of eotaxin-1 and eotaxin-2 mRNA in the lungs were almost completely dependent upon IL-13. Second, in order to address the specific role of eotaxin-2 in IL-13-induced pulmonary eosinophilia, we generated eotaxin-2 gene-deficient mice by homologous recombination. Notably, in contrast to observations made in eotaxin-1-deficient mice, eotaxin-2-deficient mice had normal base-line eosinophil levels in the hematopoietic tissues and gastrointestinal tract. However, following intratracheal IL-13 administration, eotaxin-2-deficient mice showed a profound reduction in airway eosinophilia compared with wild type mice. Most interestingly, the level of peribronchial lung tissue eosinophils in IL-13-treated eotaxin-2-deficient mice was indistinguishable from wild type mice. Furthermore, IL-13 lung transgenic mice genetically engineered to be deficient in eotaxin-2 had a marked reduction of luminal eosinophils. Mechanistic analysis identified IL-13-induced eotaxin-2 expression by macrophages in a distinct lung compartment (luminal inflammatory cells) compared with eotaxin-1, which was expressed solely in the tissue. Taken together, these results demonstrate a cooperative mechanism between IL-13 and eotaxin-2. In particular, IL-13 mediates allergen-induced eotaxin-2 expression, and eotaxin-2 mediates IL-13-induced airway eosinophilia.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 95%

Identification of a Cooperative Mechanism Involving Interleukin-13 and Eotaxin-2 in Experimental Allergic Lung Inflammation

Pope

Fulkerson

Blanchard

et al. 2005

Journal of Biological Chemistry

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139

124

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“…2 IL-13 is thought to induce AHR in the allergic lung by directly affecting epithelial cells 10 or by recruiting eosinophil via an IL-5-and eotaxin-dependent mechanism. 11,12 However, the transfer of eosinophils to IL-5 À/À mice overcomes the intrinsic defect in T cell IL-13 production 13 and induces the development of AHR. 8 Thus, although the role of IL-5 in AHR is controversial, [6][7][8][9][14][15][16] the relationship between eosinophils and AHR is still correlative.…”

Section: Introductionmentioning

confidence: 99%

“…8 Thus, although the role of IL-5 in AHR is controversial, [6][7][8][9][14][15][16] the relationship between eosinophils and AHR is still correlative. 8,[11][12][13] Apoptosis is an important mechanism for the maintenance of homoeostasis in the immune system. 17 Fas (CD95), the receptor signaling component of apoptosis, is expressed either constitutively or after activation in a variety of immune cells, such as T cells, B cells, monocytes/macrophages, NK cells, neutrophils, and eosinophils.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Chuang¹,

Cl²,

et al. 2004

Gene Ther

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Allergic asthma is characterized by airway hyper-responsiveness (AHR) and cellular infiltration of the airway with predominantly eosinophils and Th2 cells. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligandmediated apoptosis. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. To examine the effect of the FasL gene on airway inflammation and immune effector cells in allergic asthma, recombinant adenovirus expressing murine FasL (Ad-FasL) was delivered intratracheally into ovalbumin (OVA)-immunized mice. We found that a single administration of Ad-FasL in OVA-immunized mice significantly alleviated AHR and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-a production also decreased in AdFasL-treated OVA-immunized mice. These findings indicated that the administration of Ad-FasL to OVA-sensitized mice significantly suppressed pulmonary allergic responses. Although more studies are needed, these results suggested that Ad-FasL might be applied as an alternative therapy for allergic asthma.

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“…In animal models of allergic diseases or helminth infection, IL-5 induces a massive proliferation of eosinophil progenitors in the bone marrow (3,5), promotes eosinophil recruitment with eotaxins (6)(7)(8), and prolongs eosinophil survival in local tissues (9,10). IL-5 binds the IL-5R complex, which consists of an IL-5Ra chain specific for IL-5 and a common b-chain that is shared by the receptors for IL-3 and GM-CSF.…”

mentioning

confidence: 99%

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

Ikutani

Yanagibashi

Ogasawara

et al. 2012

The Journal of Immunology

271

208

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IL-5 is involved in a number of immune responses such as helminth infection and allergy. IL-5 also plays roles in innate immunity by maintaining B-1 B cells and mucosal IgA production. However, the identity of IL-5–producing cells has not been unambiguously characterized. In this report, we describe the generation of an IL-5 reporter mouse and identify IL-5–producing non-T lymphoid cells that reside in the intestine, peritoneal cavity, and lungs in naive mice. They share many characteristics with natural helper cells, nuocytes, and Ih2 cells, including surface Ags and responsiveness to cytokines. However, these phenotypes do not completely overlap with any particular one of these cell types. Innate non-T IL-5–producing cells localized most abundantly in the lung and proliferated and upregulated IL-5 production in response to IL-25 and IL-33. IL-33 was more effective than IL-25. These cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated by IL-25 and IL-33. Given that eosinophils are shown to possess antitumor activity, we studied lung tumor metastasis and showed that innate IL-5–producing cells were increased in response to tumor invasion, and their regulation of eosinophils is critical to suppress tumor metastasis. Genetic blockade or neutralization of IL-5 impaired eosinophil recruitment into the lung and resulted in increased tumor metastasis. Conversely, exogenous IL-5 treatment resulted in suppressed tumor metastasis and augmented eosinophil infiltration. These newly identified innate IL-5–producing cells thus play a role in tumor surveillance through lung eosinophils and may contribute to development of novel immunotherapies for cancer.

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IL-13 induces eosinophil recruitment into the lung by an IL-5– and eotaxin-dependent mechanism

Cited by 263 publications

References 55 publications

Identification of a Cooperative Mechanism Involving Interleukin-13 and Eotaxin-2 in Experimental Allergic Lung Inflammation

Identification of a Cooperative Mechanism Involving Interleukin-13 and Eotaxin-2 in Experimental Allergic Lung Inflammation

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

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