Tissue-resident immunity in the lung: a first-line defense at the environmental interface

Abstract

The lung is a vital organ that incessantly faces external environmental challenges. Its homeostasis and unimpeded vital function are ensured by the respiratory epithelium working hand in hand with an intricate fine-tuned tissue-resident immune cell network. Lung tissue-resident immune cells span across the innate and adaptive immunity and protect from infectious agents but can also prove to be pathogenic if dysregulated. Here, we review the innate and adaptive immune cell subtypes comprising lung-resident immunity and discuss their ontogeny and role in distinct respiratory diseases. An improved understanding of the role of lung-resident immunity and how its function is dysregulated under pathological conditions can shed light on the pathogenesis of respiratory diseases.

Keywords: Asthma; Cancer; Infections; Lung; Metastasis; Tissue-resident immunity.

Fig. 1

Location of immune tissue-resident cells in the lungs (alveoli and bronchus). Created with BioRender.com

Fig. 2

Fetal emergence and life-long maintenance of alveolar macrophages. Origin and mechanisms for a lungresident macrophage replenishment b in a healthy or diseased lung

Fig. 3

Different subtypes of tissue-resident immune cells and their cytokine production. Created with BioRender.com

Fig. 4

Models to study immune tissue-resident cells in the lung. a In vivo intravenous immune cell labelling. b In situ labelling of cells through photoconversion. c Parabiosis model. d Orthotopic lung transplantation. Created with BioRender.com