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• A new indication for IFN-α/β?
• Prenatal vitamin A affects lung function after birth
• IgE negatively affects innate immunity
• Quo vadis?
• A new receptor modulates mast cell activation

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A new indication for IFN-α/β? 

Huber et al (J Immunol 2010, doi:10.4049/jimmunol.1000469) have delivered an unexpected finding: data supporting the possible use of IFN-α/β as a therapy for asthma and other atopic diseases. Contrary to findings in mice, the authors found that IFN-α/β does, in fact, act as a negative regulator of T_H2 cell commitment. They demonstrated that IFN-α/β destabilized GATA-3 autoactivation, the process that maintains the T_H2 environment after IL-4 secretion has diminished, by decreasing GATA-3 protein levels. Additionally, Huber et al found that IFN-α/β blocked expression of prostaglandin receptors on committed T_H2 cells, suggesting that IFN-α/β might be effective in chronic atopic conditions. The authors suggested that currently available IFN-α/β therapy might be applied to allergy and asthma.

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• J. David Farrar, University of Texas Southwestern Medical Center

Dr J. David Farrar, senior author, gave us this comment: “T_H2 cells are remarkably stable in their ability to consistently secrete inflammatory cytokines because of their expression of the transcriptional master regulator GATA-3. In this study we discovered that this natural antiviral cytokine, IFN-α/β, can turn off cytokine expression in T_H2 cells by downregulating GATA-3 expression. This puts us in an excellent position to investigate novel therapeutic approaches to atopic diseases involving IFN-α/β.”

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Prenatal vitamin A affects lung function after birth 

Retinol is critical to alveolar structuring and lung development beginning in utero. Checkley et al (N Engl J Med 2010;362:1784-94) looked at the effects of vitamin A or β-carotene supplementation during pregnancy in a cohort in Nepal. Follow-up spirometry on the children of the cohort revealed mean FEV₁ and forced vital capacity (FVC) values that were higher for children whose mothers received vitamin A compared with those seen in placebo-treated control subjects. FEV₁ and FVC values were higher for those mothers treated with β-carotene, but these differences were not significant compared with values seen in control subjects. The authors also found that improved lung function in the children was related to postpartum maternal serum retinol levels.

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• William Checkley, Johns Hopkins University

Dr William Checkley, lead author on the article, had this to offer: “… To our knowledge, this is the first study that follows a cohort randomized to receive vitamin A supplementation or placebo in utero and shows that vitamin A is linked to larger lungs (by using lung function as a proxy for lung size). … The magnitude of effect observed in this study is slightly greater than that associated with preventing exposure to parental smoking in school-aged children.”

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IgE negatively affects innate immunity 

Starting from observations that increased surface expression and cross-linking of the high-affinity IgE receptor (FcεRI) on plasmacytoid dendritic cells (pDCs) were correlated with decreased expression of Toll-like receptor (TLR) 7 and 9, Gill et al (J Immunol 2010;184:5999-6006) examined the effect of this effect on pDC response to influenza A infection. The authors demonstrated that serum IgE levels and FcεRI expression on pDCs were inversely correlated to TLR-7–induced IFN-α secretion, resulting in a suppressed antiviral response. Gill et al suggested that increased serum IgE levels and increased pDC FcεRI expression, as seen in asthmatic patients, would increase susceptibility to viral infections.

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• Michelle Gill, University of Texas Southwestern Medical Center

Dr Michelle Gill, lead author, commented on the findings: “The implications … are that allergen exposure might interfere with immune responses to respiratory tract viral infections. Such interplay between allergic and antiviral responses occurs in pDCs, cells critical in directing antiviral immune responses through their capacity to secrete type I interferons.”

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Quo vadis? 

The massive data accumulating on the “-omics” of lung disease prompted a National Heart, Lung, and Blood Institute Lung Division workshop in September 2009 that addressed what needs to be done with all of it (Am J Respir Crit Care Med 2010, doi:10.1164/rccm.201002-0180PP). Led by Dr Carole Ober, the group recognized the lack of integration and applicability of genome-wide association studies of lung disease. Systems and functional analysis, epigenetics, and model systems were discussed. The group prioritized 5 areas of future research: (1) integration to describe genetic variation effects on lung function, (2) environmental effects on transcriptional and posttranscriptional regulation, (3) development of model systems to study biological complexity of gene function, (4) comparative phenotype studies of lung disease, and (5) bioinformatic research focusing on existing datasets.

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• David Schwartz, National Jewish Health

Dr David Schwartz, senior author, provided this thought: “Although enormous achievements have been made in identifying the genetic basis … of lung diseases, … function of these genes and … basic mechanisms that link the[m] to pulmonary disease have received much less attention. Innovative tools and … approaches in genetics, animal models of human disease, comparative genomics, gene-environment interactions, systems, and computational biology are now sufficiently mature to rigorously explore the function and key pathways involved. …”

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A new receptor modulates mast cell activation 

Hitomi et al (Nat Immunol 2010;11:601-7) characterized a new mast cell receptor, Allergin-1, that inhibits IgE-mediated acute anaphylaxis. Coligation of Allergin-1 and the high-affinity receptor FcεRI resulted in decreased mast cell degranulation. The authors reported that Allergin-1 recruited Src homology domain 2–containing protein tyrosine phosphatases 1 and 2, which prevented activation of FcεRI. Additionally, they demonstrated that this inhibitory effect occurs in vivo, suppressing type I hypersensitivity reactions in mice. Hitomi et al found Allergin-1 on murine and human dendritic cells, macrophages, neutrophils, and human peripheral basophils.

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• Satoko Tahara-Hanaoka, University of Tsukuba

We heard from Dr Satoko Tahara-Hanaoka, co–lead author: “The FcεRI-mediated signal is involved in all the allergic responses by mast cells and basophils. Therefore Allergin-1 might be a good target for the therapy of a variety of allergic diseases because coligation of Allergin-1 with FcεRI resulted in inhibition of FcεRI-mediated degranulation from mast cells. Allergin-1 also shed[s] light on the regulatory mechanism of human basophil activation.”