IL-13 and IFN-γ: Interactions in Lung Inflammation

Ford, Jean G.; Rennick, Donna; Donaldson, Debra D.; Venkayya, Rajeev; McArthur, Cliff; Hansell, Elisabeth; Kurup, Viswanath P.; Warnock, Martha L.; Grünig, Gabriele

doi:10.4049/jimmunol.167.3.1769

Cited by 182 publications

(162 citation statements)

References 67 publications

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“…Originally, it was believed that Th2 and Th1 responses would antagonize and thereby ameliorate each other's consequences, but our data demonstrate that strong Th1 and Th2 responses can develop simultaneously in vivo and that the development of one type of Th cell response does not necessary inhibit or prevent the development of the other. The finding of mixed Th1 and Th2 responses have previously been reported in lung inflammation models [28,29] and in a model of allergic responses to Aspergillus antigen the deletion of IL-10 resulted in exaggerated Th1 and Th2 responses in the lungs [30]. Thus, our data confirm that IL-10 may regulate both Th1 and Th2 responses at mucosal surfaces.…”

Section: Discussionsupporting

confidence: 79%

Contrasting roles for IL‐10 in protective immunity to different life cycle stages of intestinal nematode parasites

Helmby

Grencis

2003

Eur J Immunol

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Expulsion of the gastro‐intestinal nematode Trichinella spiralis is associated with a pronounced mastocytosis mediated by a T helper (Th) 2 type response involving interleukin (IL)‐4 and IL‐13. Here we demonstrate that IL‐10 is a key regulator of protective immune responses against T. spiralis in vivo. IL‐10 knockout mice or normal mice treated with a neutralizing anti‐IL‐10 receptor antibody are highly susceptible to a primary T. spiralis infection and show significantly delayed adult worm expulsion. Depletion of IL‐10 resulted in elevated Th1 and Th2 cytokine responses but significantly reduced numbers of mucosal mast cells in the jejunum. Interestingly, the increase in IFN‐γ detected in the absence of IL‐10 resulted in increased immunity to larval stages. Hence, IL‐10 has a negative effect on immunity to the tissue dwelling larval stages of T. spiralis but plays a significant biological role as an in vivo regulator of intestinal mast cell responses and is crucially involved in protection against adult stages of intestinal parasites in vivo.

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Section: Discussionsupporting

confidence: 79%

Contrasting roles for IL‐10 in protective immunity to different life cycle stages of intestinal nematode parasites

Helmby

Grencis

2003

Eur J Immunol

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“…Inflammatory changes in the lung parenchyma were evaluated as described previously (11). Briefly, the lungs were collected and fixed in 10% phosphate-buffered formalin (n ϭ 6 -10 mice/group).…”

Section: Methodsmentioning

confidence: 99%

CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge

Guedes¹,

Paulin²,

Rivero-Nava³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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-The transmembrane glycoprotein CD38 in airway smooth muscle is the source of cyclic-ADP ribose, an intracellular calcium-releasing molecule, and is subject to regulatory effects of cytokines such as interleukin (IL)-13, a cytokine implicated in asthma. We investigated the role of CD38 in airway hyperresponsiveness using a mouse model of IL-13-induced airway disease. Wild-type (WT) and CD38-deficient (CD38KO) mice were intranasally challenged with 5 g of IL-13 three times on alternate days under isoflurane anesthesia. Lung resistance (RL) in response to inhaled methacholine was measured 24 h after the last challenge in pentobarbital-anesthetized, tracheostomized, and mechanically ventilated mice. Bronchoalveolar cytokines, bronchoalveolar and parenchymal inflammation, and smooth muscle contractility and relaxation using tracheal segments were also evaluated. Changes in methacholine-induced R L were significantly greater in the WT than in the CD38KO mice following intranasal IL-13 challenges. Airway reactivity after IL-13 exposure, as measured by the slope of the methacholine dose-response curve, was significantly higher in the WT than in the CD38KO mice. The rate of isometric force generation in tracheal segments (e.g., smooth muscle reactivity) was greater in the WT than in the CD38KO mice following incubation with IL-13. IL-13 treatment reduced isoproterenol-induced relaxations to similar magnitudes in tracheal segments obtained from WT and CD38KO mice. Both WT and CD38KO mice developed significant bronchoalveolar and parenchymal inflammation after IL-13 challenges compared with naïve controls. The results indicate that CD38 contributes to airway hyperresponsiveness in lungs exposed to IL-13 at least partly by increasing airway smooth muscle reactivity to contractile agonists. interleukin-13; inflammation; asthma; eosinophil; airway smooth muscle CD38 IS A MULTIFUNCTIONAL ECTOENZYME that catalyzes the conversion of ␤-nicotinamide adenine dinucleotide to cyclic ADP-ribose (cADPR) and ADP-ribose (16). Both CD38 and its product cADPR are present in airway smooth muscle (ASM) cells and other mammalian cell types (8,26,32,39). Together with inositol 1,4,5-trisphosphate, cADPR is an important mediator of intracellular calcium ([Ca 2ϩ ] i ) release in smooth muscle cells including that of the airways (7,20,31). The dynamics of [Ca 2ϩ ] i responses to stimuli are central in the regulation of ASM contraction, bronchomotor tone, and airway caliber (33). cADPR induces Ca 2ϩ release from the sarcoplasmic reticulum through activation of ryanodine receptor channels in ASM cells (31). The [Ca 2ϩ ] i responses of human ASM cells exposed to acetylcholine, thrombin, and bradykinin are reduced by the competitive cADPR antagonist 8-bromo-cADPR in a magnitude that correlates positively with the level of CD38 expression (6).CD38-deficient (CD38KO) mice have been used to elucidate the role of CD38 in the function of several organs. CD38-generated cADPR plays a critical role in Ca 2ϩ -induced insulin secretion (21), os...

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“…T and/or B cell tolerance is not observed and robust inflammation is induced without the need for extrapulmonary Ag challenge or additional adjuvants. Despite these differences, the allergic lung disease induced by both type I and II allergens is highly stereotypical and pathologic airway obstruction is induced through a final common signaling pathway involving IL-13 (8,(23)(24)(25)(26)(27)(28).…”

Section: Efining the Immunopathologic Basis Of Allergic Inflam-mentioning

confidence: 99%

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

Kheradmand

Kiss

et al. 2002

The Journal of Immunology

290

292

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The respiratory allergens that induce experimental Th cell type 2-dependent allergic lung inflammation may be grouped into two functional classes. One class of allergens, in this study termed type I, requires priming with adjuvants remote from the lung to overcome airway tolerogenic mechanisms that ordinarily preclude allergic responses to inhaled Ags. In contrast, the other, or type II, allergen class requires neither remote priming nor additional adjuvants to overcome airway tolerance and elicit robust allergic lung disease. In this study, we show in an experimental model that diverse type II allergens share in common proteolytic activity that is both necessary and sufficient for overcoming airway tolerance and induction of pulmonary allergic disease. Inactivated protease and protease-free Ag fragments showed no allergenic potency, demonstrating that only active protease acting on endogenous substrates was essential. Furthermore, induction of airway tolerance could be aborted and allergic lung disease established by simply adding purified protease to a type I allergen. Thus, exogenous proteases are common to type II allergens and may be generally required to overcome the innate resistance of the airway to Th cell type 2 activation and allergic inflammation, raising concern for their potential contribution to diseases such as asthma.

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IL-13 and IFN-γ: Interactions in Lung Inflammation

Cited by 182 publications

References 67 publications

Contrasting roles for IL‐10 in protective immunity to different life cycle stages of intestinal nematode parasites

Contrasting roles for IL‐10 in protective immunity to different life cycle stages of intestinal nematode parasites

CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

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