Muhammad A. Pasha

Cutting edge: Notch signaling promotes the plasticity of group-2 innate lymphoid cells

The mechanisms underlying lymphocyte lineage stability and plasticity remain elusive. Recent work indicates that innate lymphoid cells (ILC) possess substantial plasticity. Whereas natural ILC2 (nILC2) produce type-2 cytokines, plastic inflammatory ILC2 (iILC2) can coproduce both type-2 cytokines and the ILC3-characteristic cytokine, IL-17. Mechanisms that elicit this lineage plasticity, and the importance in health and disease, remain unclear. In this study we show that iILC2 are potent inducers of airway inflammation in response to acute house dust mite challenge. We find that Notch signaling induces lineage plasticity of mature ILC2 and drives the conversion of nILC2 into iILC2. Acute blockade of Notch signaling abolished functional iILC2, but not nILC2, in vivo. Exposure of isolated nILC2 to Notch ligands induced Rorc expression and elicited dual IL-13/IL-17 production, converting nILC2 into iILC2. Together these results reveal a novel role for Notch signaling in eliciting ILC2 plasticity and driving the emergence of highly proinflammatory innate lymphocytes.

Group 2 innate lymphoid cells promote airway hyperresponsiveness through production of VEGFA

Author(s): Shen, Xiaofei; Pasha, Muhammad Asghar; Hidde, Kelsi; Khan, Adil; Liang, Mingwei; Guan, Wenxian; Ding, Yitao; Haczku, Angela; Yang, Qi

A literature review of the evidence that a 12% improvement in FEV1 is an appropriate cut-off for children

Abstract Introduction: A well-performed spirometry, using a change in forced expiratory volume in one second (FEV1) after albuterol, is commonly used to support the likelihood of an asthma diagnosis. The current standard, accepted by the 2007 National Heart Lung and Blood Institute Asthma Expert Panel Report-3 (EPR-3) guidelines, is a 12% improvement in the FEV1 after a bronchodilator. Objective: We sought to determine whether existing studies support or refute using a 12% improvement as a significant change in FEV1 in children and adolescents. Data sources: We reviewed the literature of children and adolescents using Medline searches to discover pertinent population studies and comparative studies that included FEV1 measurements. Result: The majority of the discovered studies suggest a less stringent improvement in FEV1 in children might be applicable. Conclusion: Supported by the published literature, we suggest an alternative interpretive strategy of expressing the results of a spirometry measurement when a diagnosis of asthma in a child is being considered using a bronchodilator response.