Exogenous interleukin-10 alleviates allergic inflammation but inhibits local interleukin-10 expression in a mouse allergic rhinitis model

Wang, Shuibin; Deng, Yuxiao; Ren, Jie; Xiao, Bokui; Liu, Zheng; Tao, Zezhang

doi:10.1186/1471-2172-15-9

Cited by 31 publications

(30 citation statements)

References 34 publications

(51 reference statements)

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“…The frequency and total number of CD4 þ T cells expressing IL-4, IL-5, and IL-13 were also significantly increased in the lung and lung-draining mediastinal lymph nodes of Cd4 Cre Il10ra fl/fl mice (Figure 2a-d and Supplementary Figure S1A-D online). Although IL-10 can also regulate both type-1 and type-17 responses following allergen challenge in the airways, 7,20 we found that the frequency of IFNg þ and IL-17A þ T cells in the lung were significantly reduced, with numbers of interferon-g (IFNg)-and IL-17A-producing CD4 þ cells unaffected by the absence of IL-10 signaling in T cells (Figure 2e,f and Supplementary Figure S1C,D). The proportion of Foxp3 þ Treg cells in the local lymph nodes were largely unaffected; however, we did observe an increase in Foxp3 þ Treg cells in the lung of Cd4 Cre Il10ra fl/fl mice (Supplementary Figure S1E,F).…”

Section: Il-10r Signaling In T Cells Regulates Th2 Cell Differentiatimentioning

confidence: 99%

“…Overall, these data provide new insight into IL-10-mediated regulation of allergic airway inflammation and identify that pathogenic Th2 cells are an important direct target of IL-10. Thus, therapeutic use of IL-10 20,38 to treat airway inflammatory conditions may directly impact antigen-reactive pathogenic T cells, expanding the broad immunosuppressive properties of IL-10.…”

Section: Il-10r Signaling Specifically In Il4 Gfp þ Th2 Cells Regulmentioning

confidence: 99%

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CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation

et al. 2017

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Interleukin-10 (IL-10) is an important regulatory cytokine required to control allergy and asthma. IL-10-mediated regulation of T cell-mediated responses was previously thought to occur indirectly via antigen-presenting cells. However, IL-10 can act directly on regulatory T cells and T helper type 17 (Th17) cells. In the context of allergy, it is therefore unclear whether IL-10 can directly regulate T helper type 2 (Th2) cells and whether this is an important regulatory axis during allergic responses. We sought to determine whether IL-10 signaling in CD4 Th2 cells was an important mechanism of immune regulation during airway allergy. We demonstrate that IL-10 directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. Mechanistically, IL-10R signaling regulated the expression of several genes in Th2 cells, including granzyme B. Indeed, IL-10 increased granzyme B expression in Th2 cells and led to increased Th2 cell death, identifying an IL-10-regulated granzyme B axis in Th2 cells controlling Th2 cell survival. This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.

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Section: Il-10r Signaling In T Cells Regulates Th2 Cell Differentiatimentioning

confidence: 99%

Section: Il-10r Signaling Specifically In Il4 Gfp þ Th2 Cells Regulmentioning

confidence: 99%

CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation

et al. 2017

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“…In recent years, the discovery of Th17 and regulatory T (Treg) cells has added additional layers of complexity to the older Th1/Th2 balance paradigm, and it has expanded our understanding of the pathogenesis of AR [3]. …”

Section: Introductionmentioning

confidence: 99%

Neutralization of interleukin-17 suppresses allergic rhinitis symptoms by downregulating Th2 and Th17 responses and upregulating the Treg response

Wang

Cao

2017

Oncotarget

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Allergic rhinitis (AR) has long been considered to predominantly involve the actions of Th2 cells, with relatively small contributions from Th1 cells. In recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered the Th1/Th2 balance paradigm more complex and expanded our understanding of the pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to induce allergen-specific Th2 cell activation, eosinophil and neutrophil accumulation, and serum IgE production in asthma; all of these features may play important roles in AR. To the best of our knowledge, only a few studies have assessed the feasibility of using IL-17 antagonists to treat AR. Thus, the principal objectives of the present study were, first, to determine the status of Th17 and Treg cells in the nasal mucosa of a mouse model of AR, and, second, to investigate the effects of IL-17 on such cells and the therapeutic efficacy of anti-IL-17 antibodies (Abs) in the context of AR. Anti-IL-17 Abs were given intranasally during the re-challenge of BALB/c mice with ovalbumin (OVA)-induced AR. We measured the numbers of nasal rubbing motions and sneezes, eosinophil and neutrophil levels, Th1, Th2, Th17, and Treg parameters in the nasal mucosa. Anti-IL-17 Abs markedly reduced the number of nasal rubbing motions and sneezes, decreased eosinophil and neutrophil infiltration, reduced Th2 and Th17 responses, and increased the Treg response. Anti-IL-17 Ab treatment protects against AR. These results will improve our understanding of AR pathogenesis and may lead to the development of novel therapeutic approaches for management of the condition.

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“…On the other hand, IL-10-deficient mice exhibit reduced numbers of intact mast cells after administration of C48/80, an effect reversed by the administration of recombinant IL-10 ( Bundoc and Keane-Myers, 2007). In addition, administration of recombinant IL-10 in an OVA-induced allergic rhinitis model reduced the influx of eosinophils and mast cells into the nasal mucosa, as well as reducing IL-5 and IL-17 in the nasal lavage fluid (Wang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Treatment with galectin-1 eye drops regulates mast cell degranulation and attenuates the severity of conjunctivitis

Mello-Bosnic

Gimenes

Oliani

et al. 2018

European Journal of Pharmacology

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Galectin-1 (Gal-1) is a β-galactoside-binding protein with diverse biological activities in the pathogenesis of inflammation, however the mechanisms by which Gal-1 modulates cellular responses in allergic inflammatory processes have not been fully determined. In this study, we evaluated the therapeutic potential of Gal-1 eye drops in an experimental model of conjunctivitis. Wistar rats received a topical application of compound (C)48/80 (100 mg/ml) into right eyes and a drop of vehicle into the contralateral eye. Another group of rats received Gal-1 (0.3 or 3 μg/eye) or sodium cromoglycate (SCG; 40 mg/ml) in both eyes and, after 15 min, right eye was challenged with C48/80. Conjunctivitis-induced by C48/80 was characterized by severe eyelid oedema and tearing, but clinical signs were ameliorated by eye drop doses of both Gal-1 (0.3/3 μg) and SCG. As expected, an increased proportion of degranulated mast cells (62%, P < 0.01) and lower histamine levels were observed after 6 h of C48/80 challenge, compared to control (32%). This effect was abrogated by Gal-1 and SCG, which reduced mast cell degranulation (31-36%), eosinophil migration and eosinophil peroxidase levels in the eyes. Gal-1 (3 μg) and SCG treatments also decreased IL-4 levels, as well as activation of mitogen activated protein kinases compared to untreated C48/80 eyes. Our findings suggest that Gal-1 eye drops represent a new therapeutic strategy for ocular allergic inflammation.

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Exogenous interleukin-10 alleviates allergic inflammation but inhibits local interleukin-10 expression in a mouse allergic rhinitis model

Cited by 31 publications

References 34 publications

CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation

CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation

Neutralization of interleukin-17 suppresses allergic rhinitis symptoms by downregulating Th2 and Th17 responses and upregulating the Treg response

Treatment with galectin-1 eye drops regulates mast cell degranulation and attenuates the severity of conjunctivitis

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