Natural killer cell NKG2D and granzyme B are critical for allergic pulmonary inflammation⋆

Farhadi, Nazanin; Lambert, Laura; Triulzi, Chiara; Openshaw, Peter; Guerra, Nadia; Culley, Fiona J.

doi:10.1016/j.jaci.2013.09.048

Cited by 44 publications

(49 citation statements)

References 63 publications

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“…NK cells have been shown to be capable of augmenting or suppressing the development of allergic lung inflammation (15, 17, 36). We thus evaluated whether the presence of increased numbers of pNK cells evident in the IP −/− mice impacts lung mucosal immune responses in these animals.…”

Section: Resultsmentioning

confidence: 99%

“…NK cells residing in the lung mucosal tissue have been described previously, however, their relationship to conventional circulating NK cells remains unclear (11–13). Previous reports have investigated the effect of NK cells on allergic lung inflammation with contradictory findings, with some instances inhibiting allergic lung inflammation (14, 15) and in others promoting eosinophilic inflammation (16, 17). Importantly, NK cells are responsive to a range of endogenously produced eicosanoids which include Resolvin-E1 (18), Lipoxin-A4 (19), PGD 2 (20), PGE 2 (21) and leukotrienes (22).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen

Simons

Ferrini

Carvalho

et al. 2017

The Journal of Immunology

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In allergic asthma, inhalation of airborne allergens such as house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (IP−/−) were compared to wild type (WT) mice. Surprisingly, IP−/− mice had increased numbers of pulmonary CD3−NK1.1+Ly49b+ NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared to WT animals. This phenomenon was associated with elevated CX3CL1 levels in the airways of IP−/− mice and treatment with a neutralizing antibody to CX3CL1 reduced IFN-γ production by the lung NK cells. Remarkably, IP−/− mice were less responsive to HDM challenge than WT counterparts since intranasal instillation of the allergen induced markedly reduced levels of airway eosinophils, CD4+ lymphocyte infiltration and mucus production, as well as depressed levels of CCL2 chemokine and Th2 cytokines. NK cells were responsible for such attenuated responses since depletion of NK1.1+ cells in IP−/− mice restored both the HDM-induced lung inflammation and ILC2 numbers, while transfer of CD3−NK1.1+ NK cells into the airways of WT hosts suppressed the inflammatory response. Collectively, these data demonstrate a hitherto unknown role for PGI2 in regulating the number and properties of NK cells resident in lung tissue and reveal a role for NK cells in limiting lung tissue ILC2s and preventing allergic inflammatory responses to inhaled HDM allergen.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen

Simons

Ferrini

Carvalho

et al. 2017

The Journal of Immunology

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“…NK cell recruitment and activation is primarily mediated by epithelial cell release of IL-15, which increases in the nasal mucosa within a few days after HRV challenge 137 . The relevance of this response to post-viral airway disease is uncertain, but NK cell expression of NK group 2 member D (NKG2D; also known as KLRK1) and granzyme B was required for the allergic response to house dust mite extract in mice 138 . Other work showed that IL-17-producing LIN − THY1.2 + ILC3s were required for airway hyperreactivity in a mouse model of asthma that was associated with obesity 139 .…”

Section: Innate Immune Cellsmentioning

confidence: 99%

The role of airway epithelial cells and innate immune cells in chronic respiratory disease

et al. 2014

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An abnormal immune response to environmental agents is generally thought to be responsible for causing chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Based on studies of experimental models and human subjects, there is increasing evidence that the response of the innate immune system is crucial for the development of this type of airway disease. Airway epithelial cells and innate immune cells represent key components of the pathogenesis of chronic airway disease and are emerging targets for new therapies. In this Review, we summarize the innate immune mechanisms by which airway epithelial cells and innate immune cells regulate the development of chronic respiratory diseases. We also explain how these pathways are being targeted in the clinic to treat patients with these diseases.

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“…A manuscript by Farhadi et al provided insight into mechanisms of NK cell activation by allergens [13]. The investigators started their story by demonstrating that that airway inflammation in the house dust mite (HDM)-induced model of asthma was dependent on NKG2D.…”

Section: Nk Cells In Mouse Models Of Asthmamentioning

confidence: 99%

Natural killer cells in asthma

Górska

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review to discuss current knowledge on natural killer (NK) cells in asthma. Recent findings It is now well accepted that NK cell activities go beyond cancer immune surveillance and anti-viral defense. Recent reports indicate that NK cells are activated in response to allergens in vivo. NK cells promote allergic sensitization, type-2 immune response, development of eosinophilic inflammation and airway hyperresponsiveness. NK cells are activated by RSV and other respiratory viruses. When infection occurs in the setting of active allergic inflammation, NK cells augment its magnitude and contribute to asthma exacerbations. Pro-asthma activities of NK cells can be programmed during embryogenesis through maternal exposure to environmental pollutants. Prenatally-programmed NK cells produce type-2 and type-3 cytokines and mediate asthma predisposition. NK cells can also act as asthma antagonists. NK cells contribute to the resolution of inflammation through suppression of antigen-specific CD4+ T cells and type-3 immunity. When viral infection occurs in naïve mice prior to allergic sensitization, NK cells antagonize type-2 immunity and prevent development of asthma. Summary NK cells are non-redundant participants of allergic inflammation. The environmental context determines whether NK cells act as protagonists or antagonists.

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Natural killer cell NKG2D and granzyme B are critical for allergic pulmonary inflammation⋆

Cited by 44 publications

References 63 publications

PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen

PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen

The role of airway epithelial cells and innate immune cells in chronic respiratory disease

Natural killer cells in asthma

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