News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2016)

Airway plasmacytoid dendritic cells (pDCs) can play a protective role in asthma, and IL-25, an epithelium-derived cytokine, has been implicated in the pathogenesis of allergic diseases and airway viral responses. However, the effects of inhaled allergens on expression of the IL-25 receptor (IL-17RB) by myeloid dendritic cells (mDCs) and pDCs and the effects of IL-25 on pDCs are unknown. Tworek et al (Am J Respir Crit Care Med 2016;193:957-64) evaluated allergen-induced changes in IL-17RB expression by mDCs and pDCs and investigated the effects of IL-25 on pDCs in patients with mild atopic asthma. The authors show that IL-17RB is upregulated on blood and sputum mDCs and pDCs after allergen inhalation. Moreover, IL-25 modulates pDC function through an effect on Toll-like receptor 9 expression, suggesting that IL-25 might be an important link between innate and adaptive immune responses. Future studies of the effects of an anti–IL-25 mAb on allergen-induced changes in dendritic cell numbers and function and the associated airway inflammation in patients with allergy and asthma will help clarify its role.IL-25 might be an important link between innate and adaptive immune responses IL-25 might be an important link between innate and adaptive immune responses We asked author Paul O’Byrne, MB, FRCP(C), FRCS from McMaster University in Ontario, Canada, about this study. He responded, “Respiratory viral infections are the most important cause of asthma exacerbations. The risk of a viral-induced asthma exacerbation is much higher in atopic individuals exposed to an environmental allergen. This study helps explain the roles of IL-25 and pDCs in causing the interaction that occurs between viral respiratory infections and environmental allergen exposure resulting in asthma exacerbations.” The skin is a site of constant dialog between the immune system and commensal bacteria. However, the molecular mechanisms that allow us to tolerate the presence of skin commensals without eliciting destructive inflammation are unknown. Using a model system to study the antigen-specific response to Staphylococcus epidermidis, Scharschmidt et al (Immunity 2015;43:1011-21) demonstrated that skin colonization during a defined period of neonatal life was required for establishing immune tolerance to commensal microbes. This crucial window was characterized by an abrupt influx of highly activated regulatory T (Treg) cells into neonatal skin. Furthermore, the selective inhibition of this Treg cell wave completely abrogated tolerance. Thus the host-commensal relationship in the skin relied on a unique Treg cell population that mediated tolerance to bacterial antigens during a defined developmental window. These results suggest that the cutaneous microbiome composition in neonatal life is crucial in shaping adaptive immune responses to commensals and that disrupting these interactions might have enduring health implications.The cutaneous microbiome composition in neonatal life is crucial The cutaneous microbiome composition in neonatal life is crucial The current understanding of immunology was largely defined in laboratory mice. However, these animals live in abnormally hygienic, specific pathogen-free barrier facilities and, like newborn human subjects, lack effector-differentiated and mucosally distributed memory T cells. Beura et al (Nature 2016;532:512-6) show that these T-cell populations are present in free-living barn populations of both feral and pet store mice with diverse microbial experience and were induced in laboratory mice after cohousing with pet store mice. Altering the living conditions of laboratory mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult mice and human subjects rather than neonates, altered resistance to a bacterial infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of the environment on the basal immune state and response to infection and could provide a relevant tool for modeling immunologic events in free-living organisms. These and other findings challenge the medical research community to reconsider the way in which experimental mice are maintained, moving away from relatively sterile conditions back to “dirty” conditions. ∗Image credit: Tiia Monto (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons (left panel) and by Rama (Own work) [CeCILL (http://www.cecill.info/licences/Licence_CeCILL_V2-en.html) or CC BY-SA 2.0 fr (http://creativecommons.org/licenses/by-sa/2.0/fr/deed.en)], via Wikimedia Commons (right panel).These findings challenge the medical research community to reconsider the way in which experimental mice are maintained These findings challenge the medical research community to reconsider the way in which experimental mice are maintained We asked Stephen Jameson, PhD, of the University of Minnesota (Minneapolis), co-corresponding author on the report, to comment: “While not a replacement for current mouse models, studies on ‘dirty’ mice provide an opportunity to evaluate how natural exposure to normal mouse pathogens and commensal microbes impacts the immune response to vaccines, tumors and transplants, as well as the incidence of allergic and autoimmune diseases.” The age at which allergenic foods should be introduced into the diets of breast-fed infants is unclear. Perkin et al (N Engl J Med 2016;374:1733-43). evaluated whether the early introduction of allergenic foods in the diets of breast-fed infants would protect against the development of food allergy. Exclusively breast-fed infants at 3 months of age were assigned to an early introduction group of 6 allergenic foods (peanut, cooked egg, cow’s milk, sesame, whitefish, and wheat) or to a standard introduction group (exclusive breast-feeding to approximately 6 months of age). The authors show that food allergy to 1 or more of the 6 intervention foods developed in 7.1% of the participants in the standard-introduction group and in 5.6% of those in the early-introduction group (P = .32). The prevalence of any food allergy was significantly lower in the early-introduction group than in the standard-introduction group (2.4% vs 7.3%, P = .01), as was the prevalence of peanut allergy (0% vs 2.5%, P = .003) and egg allergy (1.4% vs 5.5%, P = .009). Furthermore, the consumption of 2 g/wk of peanut or egg white protein was associated with a significantly lower prevalence of these respective allergies compared with less consumption. This study suggests that the possibility of preventing food allergy by means of the early introduction of multiple allergenic foods in healthy breast-fed infants might depend on adherence and dose.The prevalence of any food allergy was significantly lower in the early-introduction group The prevalence of any food allergy was significantly lower in the early-introduction group Medical errors are now the third leading cause of death in the USA–250,000 per year (BMJ 2016;353:i2139).News items were written by medical writer Kristina Bielewicz, MS.Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com. News items were written by medical writer Kristina Bielewicz, MS. Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com.