Advancing Lung Immunology Research: An Official American Thoracic Society Workshop Report

Abstract

The mammalian airways and lungs are exposed to a myriad of inhaled particulate matter, allergens, and pathogens. The immune system plays an essential role in protecting the host from respiratory pathogens, but a dysregulated immune response during respiratory infection can impair pathogen clearance and lead to immunopathology. Furthermore, inappropriate immunity to inhaled antigens can lead to pulmonary diseases. A complex network of epithelial, neural, stromal, and immune cells has evolved to sense and respond to inhaled antigens, including the decision to promote tolerance versus a rapid, robust, and targeted immune response. Although there has been great progress in understanding the mechanisms governing immunity to respiratory pathogens and aeroantigens, we are only beginning to develop an integrated understanding of the cellular networks governing tissue immunity within the lungs and how it changes after inflammation and over the human life course. An integrated model of airway and lung immunity will be necessary to improve mucosal vaccine design as well as prevent and treat acute and chronic inflammatory pulmonary diseases. Given the importance of immunology in pulmonary research, the American Thoracic Society convened a working group to highlight central areas of investigation to advance the science of lung immunology and improve human health.

Keywords: allergy and immunology; lung diseases; mucosal immunity.

Figure 1.

Model of airway sensing and memory. The airway epithelium consists of heterogeneous cell types that perform barrier functions, including mucociliary clearance, as well as immunosurveillance. Barrier function breach, such as occurs with respiratory pathogens, is sensed by specific epithelial cell subsets and other sensors, including neurons and innate immune populations. Defining how various immune sensors respond and integrate signals in distinct contexts to initiate an immune response represents a critical area of investigation. After an immune response, inflammatory memory is retained in various cell populations and niches, including tissue-resident memory T and B cells in adventitial niches or inducible bronchus-associated lymphoid tissue, which can promote host protection or immunopathology. The signals regulating the development and maintenance of tissue-resident memory remain an active area of investigation. Illustration created in Biorender.com. Brm = tissue-resident memory B cell; DC = dendritic cell; Gob = goblet cell; iBALT = inducible bronchus-associated lymphoid tissue; ILC = innate lymphoid cell; MCC = mucociliary clearance; Mϕ = macrophage; NE = neuroendocrine cell; Treg = regulatory T cell; Trm = tissue-resident memory T cell.