Monday, November 28, 2016
Over the past 25 years, the rates of both obesity and asthma have increased dramatically. These are related to one another, with a 92% increased risk of asthma in people whose body mass index (BMI) exceeds 30 kg/m2. People who do lose weight through bariatric surgery or dietary restriction, tend to show improvement in their bronchial hyperresponsiveness, the major feature of asthma. The reason for this correlation is not well understood. IL-33, a intercellular messenger that skews helper T cells towards allergies, is produced by fat cells. IL33 also induces type 2 and type 3 innate lymphoid cells (ILC2 and ILC3), two more recently identified sets of immune cells in fat and the lungs.
In this month’s issue of the Journal of Allergy and Clinical Immunology, Everaere and colleagues use mouse models to investigate the roles of innate lymphoid cells in the correlation between asthma and obesity (J Allergy Clin Immunol 2016; 138(5): 1309-1318). The mice were given a high-fat diet to induce obesity and were then sensitized to dust mites. Their lung secretions were isolated by bronchoaveolar lavage (BAL) and checked for various proteins, RNA, and cell types by histology and flow cytometry.
They found that nonsensitized obese mice had increased ILC counts and tissue eosinophils, cells that mediate damage in asthma, compared to lean mice. These mice also had high IL33 and IL-1-Beta levels. When ILCs were depleted using an anti-CD90 antibody, there was decreased infiltration by cells that prompt allergic inflammation, such as TH2 and TH17 cells.
Altogether, these results suggest that ILC2s and ILC3s mediate and exacerbate airway inflammation in obese mice. This opens the possibility of using anti-IL5 antibodies in treating asthma for obese patients.
Wednesday, November 23, 2016
Allergic skin sensitization promotes eosinophilic esophagitis through the IL-33–basophil axis in mice
Eosinophilic esophagitis (EoE) is an allergic disorder seen in approximately 1 out of 2000 people in the United States. Young children often present with vomiting and failure to thrive, while older children and adults may have difficulties swallowing, food impaction, or strictures in their esophagus. Despite increasing awareness and diagnosis, the etiology remains unclear. Past studies support the role of a subset of Helper T-cells, called TH2 cells, which are also present in many other allergic diseases, including atopic dermatitis (AD). In fact, approximately half of patients with EoE have AD. But why is that so?
In this month’s issue of the Journal of Allergy and Clinical Immunology, Venturelli and colleagues investigate the role of abnormal skin barriers in the development of EoE, and, in particular, the role of IL-33, a chemical messenger whose levels are elevated in both EoE and AD (J Allergy Clin Immunol 2016; 138(5): 1367-1380). They also investigated the role of ST2, an IL-33 receptor found on basophils using a mouse model. They applied ovalbumin to the mechanically injured skin of wild-type mice, and then to the skin of mice lacking filaggrin (ft/ft), which tend to develop AD-like skin lesions. They then challenged both strains of mice with intra-nasal ovalbumin. The esophagi of these mice were then examined microscopically and through advanced genetic analytic techniques.
They found that a disrupted skin barrier (by tape stripping or a Filaggrin gene mutation) promotes the development of EoE, and that this is mediated by IL-33, ST2, and basophils. They also reported that patients with EoE have increased ST2 in their esophagus. Their findings suggest that IL-33 could be a potential link between AD and EoE. This is an important step in understanding how patients with AD and filaggrin deficiency tend to develop EoE. Just as importantly, it may prompt development of new medications that block IL-33 or ST2, which could be effective targets for EoE.
Tuesday, November 22, 2016
Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: A multicenter study in Europe, Asia, and Oceania
Chronic Rhinosinusitis is a chronic disease of the sinuses that’s seen in up to 27% of adults in Europe and 14% in the United States. Grouped in two categories, chronic rhinosinusitis with nasal polyposis (CRwNP) and chronic rhinosinusitis without nasal polyposis (CRsNP), chronic rhinosinusitis appears to be mediated by very distinct immune mechanisms. Interestingly, there are differences in the clinical presentations between ethnic groups as well as in the types and levels of cytokines produced by immune cells.
Wang and colleagues expand upon this prior knowledge by looking at 435 patients with chronic rhinosinusitis, and comparing them to 138 control subjects (J Allergy Clin Immunol 2016; 138(5): 1344-1353). They were recruited from six regions covering Europe, Australia, and Asia. They checked the levels of cytokines, inflammatory mediators and IgE, the antibody mediating allergies, from the mucosa of subjects. The levels of these parameters were then compared among the different subjects.
They found that there was a large variety of expression of these cytokines among the different subjects in various regions. This suggests that chronic rhinosinusitis is more of an umbrella term and that there are actually many different endotypes of patients with chronic rhinosinusitis.