Regulatory T cells and IL-10 in allergic inflammation

Hawrylowicz, Catherine M.

doi:10.1084/jem.20052211

Cited by 159 publications

(121 citation statements)

References 37 publications

(41 reference statements)

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“…A second candidate cell for the production of IL-10 is Treg cells, as production of IL-10 by Treg cells has been suggested to play a central role in control of allergic airway disease (49). However, depletion of Treg cells by anti-CD25 treatment did not lead to reduction of IL-10 levels in our experiments, strongly suggesting that Treg cells are not the main source of IL-10 in our setting.…”

Section: Discussioncontrasting

confidence: 50%

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

Schnoeller

Rausch

Pillai

et al. 2008

The Journal of Immunology

226

196

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The coincidence between infections with parasitic worms and the reduced prevalence of allergic disease in humans and in animal models has prompted the search for helminth molecules with antiallergic and antiinflammatory potential. We report herein that filarial cystatin, a secreted protease inhibitor of filarial nematodes, suppresses Th2-related inflammation and the ensuing asthmatic disease in a murine model of OVA-induced allergic airway responsiveness. Treatment with recombinant filarial cystatin inhibited eosinophil recruitment, reduced levels of OVA-specific and total IgE, down-regulated IL-4 production, and suppressed allergic airway hyperreactivity when applied during or after sensitization and before challenge with the allergen. Depletion of macrophages by clodronate-containing liposomes prevented the curative effects and restored the levels of infiltrating cells, IgE, and allergic airway reactivity. Blocking of IL-10 by application of anti-IL-10 receptor Abs restored the reduced number of infiltrating cells and the levels of OVA-specific IgE. In contrast, depletion of regulatory T cells by anti-CD25 Abs had only limited effects. Cystatin also modulated macrophage-mediated inflammation in a murine model of dextran sulfate sodium-induced colitis, leading to reduction of inflammatory infiltrations and epithelial damage. Our data demonstrate that treatment with a single helminth protein can exert the antiallergic effects of helminth infections.

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Section: Discussioncontrasting

confidence: 50%

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

Schnoeller

Rausch

Pillai

et al. 2008

The Journal of Immunology

226

196

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“…The development of allergen-specific T-regulatory cells appears to be a critical event in the control of a balanced immune response to allergens and IL-10 by its immune modulating and antiinflammatory effects occupies a crucial role in this process (34,35). Therefore, in our model the offspring not only showed a suppressed Th1-response and a resulting dominance of the Th2-branch, but simultaneously a lack of immune-modulating cytokines of T-regulatory cells.…”

Section: Discussionmentioning

confidence: 91%

Anti‐ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2‐bias in their offspring

Schöll¹,

Ackermann²,

Özdemir

et al. 2007

FASEB j.

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The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1-and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. Keywordssensitization against food; sucralfate; digestion; children; lactation The incidence of food allergies has been steadily increasing in the past decades and these allergies now affect ~3.5-4% of the adult population in the United States(1) and ~2.2-5.5% of children in the first year of life (2). Apart from several environmental influence factors, no genuine explanation accounts for this high number of children with food sensitization. It is known that the risk for sensitization in the offspring is higher when one or both parents, but especially when the mother is atopic (3). This may be due to hereditary factors, but an atopic mother may also transfer factors that directly bias the immune response of the infant to an allergic phenotype. For the adult population, we could show in previous studies that the risk to develop sensitization against food allergens increases with the usage of acid-suppressing drugs (4, 5), which are applied for the treatment of dyspeptic disorders such as gastric reflux, heartburn, and gastritis. We suggested that the hindered peptic digestion due to the elevated pH in the stomach leaves bigger fragments of alimentary proteins. These proteins could then elicit allergy due to persistence of their native conformation. © FASEBApproximately two-thirds of pregnant women suffer from heartburn and reflux due to low esophageal sphincter pressure, which is caused by changes of the hormone status (6). For their treatment, Richter suggested a step-up algorithm beginning with lifestyle modifications and dietary changes. As the first-line medical treatment antacids and sucralfate are used (7). The same review states that actually ~30-50% of women use antacids to relieve heartburn and other acid-reflux symptoms during pregnancy. For sucralfate, another nonabsorbable drug like antaci...

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“…Each of these cell types has defined roles in asthma (17)(18)(19)(20). To determine whether Ova treatment of Mfge8 −/− mice affected T-cell differentiation, we isolated lymphocytes from the lung and measured cytokine production (or expression of FoxP3 for Treg cells).…”

Section: Resultsmentioning

confidence: 99%

Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction

Kudo

Soltani

Sakuma

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Airway obstruction is a hallmark of allergic asthma and is caused primarily by airway smooth muscle (ASM) hypercontractility. Airway inflammation leads to the release of cytokines that enhance ASM contraction by increasing ras homolog gene family, member A (RhoA) activity. The protective mechanisms that prevent or attenuate the increase in RhoA activity have not been well studied. Here, we report that mice lacking the gene that encodes the protein Milk Fat Globule-EGF factor 8 (Mfge8 −/− ) develop exaggerated airway hyperresponsiveness in experimental models of asthma. Mfge8 −/− ASM had enhanced contraction after treatment with IL-13, IL-17A, or TNF-α. Recombinant Mfge8 reduced contraction in murine and human ASM treated with IL-13. Mfge8 inhibited IL-13-induced NF-κB activation and induction of RhoA. Mfge8 also inhibited rapid activation of RhoA, an effect that was eliminated by an inactivating point mutation in the RGD integrin-binding site in recombinant Mfge8. Human subjects with asthma had decreased Mfge8 expression in airway biopsies compared with healthy controls. These data indicate that Mfge8 binding to integrin receptors on ASM opposes the effect of allergic inflammation on RhoA activity and identify a pathway for specific inhibition of ASM hypercontractility in asthma.calcium sensitivity | lactadherin

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Regulatory T cells and IL-10 in allergic inflammation

Cited by 159 publications

References 37 publications

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

Anti‐ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2‐bias in their offspring

Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction

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