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Targeting the Networks that Underpin Contiguous Immunity in Asthma and Chronic Obstructive Pulmonary Disease

Academic Units of ¹ Respiratory Medicine and ² Infectious Diseases, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom; and ³ Allergy and Inflammation Research, Division of Infection, Inflammation, and Repair, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom

Correspondence and requests for reprints should be addressed to Professor Ian Sabroe, Ph.D., F.R.C.P, Academic Unit of Respiratory Medicine, School of Medicine and Biomedical Sciences, University of Sheffield, L Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. E-mail: i.sabroe{at}sheffield.ac.uk

ABSTRACT

Recent advances in the field of innate immunity have driven an important reappraisal of the role of these processes in airway disease. Various strands of evidence indicate that resident cells, such as macrophages and epithelial cells, have central importance in the initiation of inflammation. Macrophage activation has the potential to regulate not just typical aspects of innate immunity but also, via a variety of intricate cell–cell networks, adaptive responses and responses characterized by Th2-type cytokine production. In turn, such adaptive immune processes modify the phenotype and function of the innate immune system. Cooperative responses between monocytic cells and tissue cells are likely to be crucial to the generation of effective inflammatory responses, and a realization of the importance of these networks is providing a new way of identifying antiinflammatory therapies. Importantly, the repeated cycles of allergic and nonallergic inflammation that comprise chronic human airway disease are not necessarily well described by current terminology, and we propose and describe a concept of contiguous immunity, in which continual bidirectional cross-talk between innate and adaptive immunity describes disease processes more accurately.

Key Words: asthma • chronic obstructive pulmonary disease • innate immunity • inflammation • macrophages

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