Regulation of immunological homeostasis in the respiratory tract

• Published in: Nature reviews. Immunology Vol. 8; no. 2; pp. 142 - 152
• Main Authors: Holt, Patrick G, Strickland, Deborah H, Wikström, Matthew E, Jahnsen, Frode L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2008; Nature Publishing Group
• Subjects: Antigens; Biomedical and Life Sciences; Biomedicine; Blood; Cardiopulmonary system; Cell Movement; Childrens health; Dendritic cells; Health aspects; Homeostasis; Homeostasis - immunology; Humans; Immune response; Immune system; Immunology; Lung - immunology; Lungs; Lymphatic system; Lymphocytes; Medical research; Oxygenation; Physiological aspects; Respiratory Mucosa - immunology; Respiratory organs; Respiratory tract; review-article; Surface area; T cells; T-Lymphocytes - immunology; Western Australia
• ISSN: 1474-1733; 1474-1741
• DOI: 10.1038/nri2236

Key Points
The central theme of this Review is how the respiratory immune system maintains a strong defence against incoming pathogens, while avoiding the pathogenic consequences of inappropriate responses to much more frequent exposures to airborne non-pathogenic antigens.
The effects of the anatomical organization of the immune system at different levels of the respiratory tract emphasizes the defining immunological features of individual tissue compartments within the conducting airways versus the lung parenchyma.
The induction of the immune response in the lungs involves complicated cellular dynamics, in particular involving the control of tissue-specific homing via mechanisms related to the functioning of the common mucosal immune system.
Pattern-recognition receptors, including Toll-like receptors, have a central role in local immune surveillance.
Individual cell types have specialized roles in maintaining local immunological homeostasis, so it is important to elucidate their nature and function(s). The key players are lung macrophage populations, airway epithelial cells, and in particular dendritic cell (DC) subpopulations and regulatory T cells; natural-killer-cell populations and mast cells are also important.
There is an emerging role(s) for T helper 17 (T
H
17) cells, and 'inflammatory' T
H
2 cells, for which differentiation is driven via epithelial-cell-derived thymic stromal lymphopoietin signals that act together with DCs.
Aspects of the pathogenesis of atopic asthma are an exemplary model of how these overlapping regulatory systems interact to maintain local homeostasis. A classic example is the complex interplay among airway mucosal DCs, adjacent macrophages, incoming recirculating memory T
H
cells and subsequently recruited regulatory T cells in controlling the intensity and duration of local recall responses to inhaled allergen.
The immune system has evolved specific mechanisms to deal with the unique problems encountered in the specialized microenvironment of the lung. This Review discusses the key mechanisms through which the local immune system maintains immunological homeostasis in the lung while preserving the integrity of the gas-exchange surfaces.
The respiratory tract has an approximate surface area of 70 m
2
in adult humans, which is in virtually direct contact with the outside environment. It contains a uniquely rich vascular bed containing a large pool of marginated T cells, and harbours a layer of single-cell-thick epithelial tissue through which re-oxygenation of blood must occur uninterrupted for survival. It is therefore not surprising that the respiratory tract is never more than a short step away from disaster. We have only a partial understanding of how immunological homeostasis is maintained in these tissues, but it is becoming clear that the immune system has evolved a range of specific mechanisms to deal with the unique problems encountered in this specialized microenvironment.