Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology

Temann, Ulla-Angela; Ray, Prabir; Flavell, Richard A.

doi:10.1172/jci200213696

Cited by 47 publications

(22 citation statements)

References 43 publications

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“…The fact that IL-9 production was more strictly linked to the latter condition than IL-13 does not challenge the notion that IL-13 is an essential effector in asthma [32,33]. However, our data suggest that the in vitro production of IL-9, which in mice is a predominant inducer of IL-13 in vivo [34], is a more accurate marker for atopy-promoting T cell responses.…”

Section: Discussionmentioning

confidence: 45%

Allergen‐induced interleukin‐9 production in vitro: correlation with atopy in human adults and comparison with interleukin‐5 and interleukin‐13

Devos

Cormont

Vrtala

et al. 2006

Clin Experimental Allergy

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Section: Discussionmentioning

confidence: 45%

Allergen‐induced interleukin‐9 production in vitro: correlation with atopy in human adults and comparison with interleukin‐5 and interleukin‐13

Devos

Cormont

Vrtala

et al. 2006

Clin Experimental Allergy

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“…Th2 cytokines are enhanced in allergic disease and are important regulators of allergic lung responses. Several studies have demonstrated enhanced allergic responses in animals with Th2-dominated phenotypes (34)(35)(36)(37). Thus, the reported Th2 bias of H1R -/-mice might have predicted an exaggerated allergic inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

The H1 histamine receptor regulates allergic lung responses

Bryce¹

2006

Journal of Clinical Investigation

126

103

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Histamine, signaling via the type 1 receptor (H1R), has been shown to suppress Th2 cytokine production by in vitro cultured T cells. We examined the role of H1R in allergic inflammation in vivo using a murine asthma model. Allergen-stimulated splenic T cells from sensitized H1R -/-mice exhibited enhanced Th2 cytokine production. Despite this Th2 bias, allergen-challenged H1R -/-mice exhibited diminished lung Th2 cytokine mRNA levels, airway inflammation, goblet cell metaplasia, and airway hyperresponsiveness (AHR). Restoration of pulmonary Th2 cytokines in H1R -/-mice by intranasal IL-4 or IL-13 restored inflammatory lung responses and AHR. Further investigation revealed that histamine acts as a T cell chemotactic factor and defective T cell trafficking was responsible for the absence of lung inflammation. Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R. In vivo, allergen-specific WT but not H1R -/-CD4 + T cells were recruited to the lungs of naive recipients following inhaled allergen challenge. H1R -/-T cells failed to confer airway inflammation or AHR observed after transfer of WT T cells. Our data establish a role for histamine and H1R in promoting the migration of Th2 cells into sites of allergen exposure.

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“…In mice, overexpression of IL-9 in the lung induces an asthma-like phenotype in an IL-13-dependent manner (Temann et al, 1998, 2002, 2007) and blocking of IL-9 reduces airway hypersensitivity (Kung et al, 2001; Cheng et al, 2002). IL-9 induces mucous production, goblet cell hyperplasia, and other features of airway remodeling (Townsend et al, 2000; Kearley et al, 2011), effects shared by IL-13 via goblet cell hyperplasia (Wynn, 2003) and IL-5 via eosinophilia (Cho et al, 2004).…”

Section: Protease-induced Allergic Responses and Il-9 Producing Cellsmentioning

confidence: 99%

Role of Innate Lymphocytes in Infection and Inflammation

Koyasu

Moro

2012

Front. Immun.

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Cooperation between the innate and adaptive immune responses is critical for enabling protective immunity against various invading microbes. Distinct types of effector T cells have different functions in adaptive immune responses. Th1 cells play important roles in the control of intracellular bacteria by producing IFN-γ to activate macrophages and in anti-viral immunity by producing IFN-γ and activating cytotoxic T lymphocytes. Th2 cell-derived cytokines are important in activating mast cells, eosinophils, and goblet cells in anti-helminth immunity. Th17 cells are pivotal for the inflammatory response mediated by neutrophils, which resists extracellular bacterial infection. In all cases, it is critical that the innate immune responses limit the growth and expansion of invading microbes until antigen-specific adaptive immune responses are established. Recent studies have identified multiple subsets in innate lymphocytes corresponding to previously defined Th subsets. Classical natural killer cells, RORγ+ lymphoid tissue inducer-related cells, and Th2-type innate lymphocytes play distinct roles in innate immune responses by producing Th1, Th17, and Th2 cytokines, respectively. Cooperation between innate lymphocytes and antigen-specific T and B cells are likely important in protective immunity against distinct types of microbes. The most recently identified subset is the RORγ-independent Lin−Thy-1+IL-7R+GATA3+ innate lymphocyte subset such as natural helper (NH) cell, which is Id2- and IL-7-dependent. This population produces Th2 cytokines, most notably IL-5 and IL-13, and plays a major role in innate immune responses during anti-helminth immunity. In addition, these cells are likely involved in the pathophysiology of some types of allergic diseases. We summarize here current knowledge regarding various innate lymphocyte subsets. In particular, we focus on the Th2-type innate lymphocyte subset.

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Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology

Cited by 47 publications

References 43 publications

Allergen‐induced interleukin‐9 production in vitro: correlation with atopy in human adults and comparison with interleukin‐5 and interleukin‐13

Allergen‐induced interleukin‐9 production in vitro: correlation with atopy in human adults and comparison with interleukin‐5 and interleukin‐13

The H1 histamine receptor regulates allergic lung responses

Role of Innate Lymphocytes in Infection and Inflammation

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