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 (TH17) cells, and 'inflammatory' TH2 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 TH cells and subsequently recruited regulatory T cells in controlling the intensity and duration of local recall responses to inhaled allergen.
The respiratory tract has an approximate surface area of 70 m2 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.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Cell Death & Disease Open Access 26 July 2022
Current Osteoporosis Reports Open Access 04 May 2022
Reviews in Endocrine and Metabolic Disorders Open Access 29 January 2022
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Nelson, D. J., McMenamin, C., McWilliam, A. S., Brenan, M. & Holt, P. G. Development of the airway intraepithelial dendritic cell network in the rat from class II major histocompatibility (Ia)-negative precursors: differential regulation of Ia expression at different levels of the respiratory tract. J. Exp. Med. 179, 203–212 (1994).
Jahnsen, F. L. et al. Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge. Thorax 56, 823–826 (2001).
Stumbles, P. A. et al. Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity. J. Exp. Med. 188, 2019–2031 (1998).
Jahnsen, F. L. et al. Accelerated antigen sampling and transport by airway mucosal dendritic cells following inhalation of a bacterial stimulus. J. Immunol. 177, 5861–5867 (2006).
Rescigno, M. et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunol. 2, 361–367 (2001).
Lund, F. E. et al. B cells are required for generation of protective effector and memory CD4 cells in response to pneumocystis lung infection. J. Immunol. 176, 6147–6154 (2006).
Moyron-Quiroz, J. E. et al. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nature Med. 10, 927–934 (2004).
Strickland, D. H., Kees, U. R. & Holt, P. G. Regulation of T-cell activation in the lung: isolated lung T-cells exhibit surface phenotypic characteristics of recent activation including downmodulated TcR, but are locked into G0/G1 phase of the cell cycle. Immunology 87, 242–249 (1996).
Holt, P. G. & Sedgwick, J. D. Suppression of IgE responses following antigen inhalation: a natural homeostatic mechanism which limits sensitization to aeroallergens. Immunol. Today 8, 14–15 (1987).
Umetsu, D. T. & DeKruyff, R. H. The regulation of allergy and asthma. Immunol. Rev. 212, 238–255 (2006).
Weiner, H. L. et al. Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu. Rev. Immunol. 12, 809–837 (1994).
de Heer, H. J. et al. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J. Exp. Med. 200, 89–98 (2004).
Hintzen, G. et al. Induction of tolerance to innocuous inhaled antigen relies on a CCR7-dependent dendritic cell-mediated antigen transport to the bronchial lymph node. J. Immunol. 177, 7346–7354 (2006).
Strickland, D. H. et al. Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. J. Exp. Med. 203, 2649–2660 (2006). This study demonstrates how interactions between airway mucosal DCs and T Reg cells control the intensity and duration of T H -cell memory responses in the airways.
Bilyk, N. & Holt, P. G. Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 177, 1773–1777 (1993).
Eriksson, U. et al. Human bronchial epithelium controls TH2 responses by TH1-induced, nitric oxide-mediated STAT5 dephosphorylation: implications for the pathogenesis of asthma. J. Immunol. 175, 2715–2720 (2005).
Lambrecht, B. N. Alveolar macrophage in the driver's seat. Immunity 24, 366–368 (2006). A comprehensive review of the multifaceted immunomodulatory and effector roles of alveolar macrophages.
Thepen, T., Van Rooijen, N. & Kraal, G. Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J. Exp. Med. 170, 499–509 (1989).
Eisenbarth, S. C. et al. Lipopolysaccharide-enhanced, Toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J. Exp. Med. 196, 1645–1651 (2002). A landmark study demonstrating the role of environmental LPS in facilitating the recognition of, and host responses to, inhaled protein antigens.
Gereda, J. E. et al. Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet 355, 1680–1683 (2000).
Agace, W. W. Tissue-tropic effector T cells: generation and targeting opportunities. Nature Rev. Immunol. 6, 682–692 (2006).
Cose, S., Brammer, C., Khanna, K. M., Masopust, D. & Lefrancois, L. Evidence that a significant number of naive T cells enter non-lymphoid organs as part of a normal migratory pathway. Eur. J. Immunol. 36, 1423–1433 (2006).
Iwata, M. et al. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21, 527–538 (2004).
Kunkel, E. J. & Butcher, E. C. Plasma-cell homing. Nature Rev. Immunol. 3, 822–829 (2003).
Campbell, J. J. et al. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 400, 776–780 (1999).
Homey, B. et al. CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nature Med. 8, 157–165 (2002).
Sigmundsdottir, H. et al. DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27. Nature Immunol. 8, 285–293 (2007).
Mora, J. R. et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314, 1157–1160 (2006).
Kohlmeier, J. E. & Woodland, D. L. Memory T cell recruitment to the lung airways. Curr. Opin. Immunol. 18, 357–362 (2006). A review of control of the recruitment of recirculating memory T H cells in lung tissues.
Campbell, J. J. et al. Expression of chemokine receptors by lung T cells from normal and asthmatic subjects. J. Immunol. 166, 2842–2848 (2001).
Galkina, E. et al. Preferential migration of effector CD8+ T cells into the interstitium of the normal lung. J. Clin. Invest. 115, 3473–3483 (2005).
Kallinich, T. et al. Chemokine-receptor expression on T cells in lung compartments of challenged asthmatic patients. Clin. Exp. Allergy. 35, 26–33 (2005).
Morgan, A. J. et al. Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease. Clin. Exp. Allergy. 35, 1572–1580 (2005).
Ray, S. J. et al. The collagen binding α1β1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity 20, 167–179 (2004).
Ely, K. H., Cookenham, T., Roberts, A. D. & Woodland, D. L. Memory T cell populations in the lung airways are maintained by continual recruitment. J. Immunol. 176, 537–543 (2006).
von Garnier, C. et al. Anatomical location determines the distribution and function of dendritic cells and other APCs in the respiratory tract. J. Immunol. 175, 1609–1618 (2005).
Lambrecht, B. N., Salomon, B., Klatzmann, D. & Pauwels, R. A. Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J. Immunol. 160, 4090–4097 (1998). The first study to provide direct evidence for the central role of airway mucosal DCs in triggering T H -cell memory responses to inhaled allergen.
Demedts, I. K., Brusselle, G. G., Vermaelen, K. Y. & Pauwels, R. A. Identification and characterization of human pulmonary dendritic cells. Am. J. Respir. Cell Mol. Biol. 32, 177–184 (2005).
Schlecht, G. et al. Murine plasmacytoid dendritic cells induce effector/memory CD8+ T-cell responses in vivo after viral stimulation. Blood 104, 1808–1815 (2004).
Wikstrom, M. E. & Stumbles, P. A. Mouse respiratory tract dendritic cell subsets and the immunological fate of inhaled antigens. Immunol. Cell Biol. 85, 182–188 (2007).
Holt, P. G., Haining, S., Nelson, D. J. & Sedgwick, J. D. Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J. Immunol. 153, 256–261 (1994).
McWilliam, A. S., Nelson, D., Thomas, J. A. & Holt, P. G. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J. Exp. Med. 179, 1331–1336 (1994). A milestone study demonstrating that rapid recruitment of immature DCs into the airway mucosa represents the 'default' response to local challenge with virtually all classes of airborne environmental stimuli.
Stumbles, P. A. et al. Regulation of dendritic cell recruitment into resting and inflamed airway epithelium: use of alternative chemokine receptors as a function of inducing stimulus. J. Immunol. 167, 228–234 (2001).
Robays, L. J. et al. Chemokine receptor CCR2 but not CCR5 or CCR6 mediates the increase in pulmonary dendritic cells during allergic airway inflammation. J. Immunol. 178, 5305–5311 (2007).
Demedts, I. K., Bracke, K. R., Maes, T., Joos, G. F. & Brusselle, G. G. Different roles for human lung dendritic cell subsets in pulmonary immune defense mechanisms. Am. J. Respir. Cell Mol. Biol. 35, 387–393 (2006).
Masten, B. J. et al. Characterization of myeloid and plasmacytoid dendritic cells in human lung. J. Immunol. 177, 7784–7793 (2006).
Krug, A. et al. Interferon-producing cells fail to induce proliferation of naive T cells but can promote expansion and T helper 1 differentiation of antigen-experienced unpolarized T cells. J. Exp. Med. 197, 899–906 (2003).
Fonteneau, J.-F. et al. Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity. Blood 101, 3520–3526 (2003).
Sapoznikov, A. et al. Organ-dependent in vivo priming of naive CD4+, but not CD8+, T cells by plasmacytoid dendritic cells. J. Exp. Med. 204, 1923–1933 (2007).
Howarth, P. H. et al. Epithelially derived endothelin and nitric oxide in asthma. Int. Arch. Allergy Immunol. 107, 228–230 (1995).
Mayer, A. K. et al. Differential recognition of TLR-dependent microbial ligands in human bronchial epithelial cells. J. Immunol. 178, 3134–3142 (2007).
Pichavant, M. et al. Impact of bronchial epithelium on dendritic cell migration and function: modulation by the bacterial motif KpOmpA. J. Immunol. 177, 5912–5919 (2006).
Contoli, M. et al. Role of deficient type III interferon-λ production in asthma exacerbations. Nature Med. 12, 1023–1026 (2006).
Wark, P. A. B. et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J. Exp. Med. 201, 937–947 (2005).
Cox, G., Gauldie, J. & Jordana, M. Bronchial epithelial cell-derived cytokines (G-CSF and GM-CSF) promote the survival of peripheral blood neutrophils in vitro. Am. J. Respir. Cell Mol. Biol. 7, 507–513 (1992).
Bleck, B., Tse, D. B., Jaspers, I., Curotto de Lafaille, M. A. & Reibman, J. Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation. J. Immunol. 176, 7431–7437 (2006).
Kato, A., Truong-Tran, A. Q., Scott, A. L., Matsumoto, K. & Schleimer, R. P. Airway epithelial cells produce B cell-activating factor of TNF family by an IFN-β-dependent mechanism. J. Immunol. 177, 7164–7172 (2006).
MacLean, J. A. et al. Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity. Am. J. Pathol. 148, 657–666 (1996).
Jakubzick, C., Tacke, F., Llodra, J., van Rooijen, N. & Randolph, G. J. Modulation of dendritic cell trafficking to and from the airways. J. Immunol. 176, 3578–3584 (2006).
Holt, P. G. et al. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J. Exp. Med. 177, 397–407 (1993).
Munger, J. S. et al. The integrin αvβ6 binds and activates latent TGFβ1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96, 319–328 (1999).
Takabayashi, K. et al. Induction of a homeostatic circuit in lung tissue by microbial compounds. Immunity 24, 475–487 (2006).
Morris, D. G. et al. Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema. Nature 422, 169–173 (2003).
Gwinn, M. R. & Vallyathan, V. Respiratory burst: role in signal transduction in alveolar macrophages. J. Toxicol. Environ. Health B Crit. Rev. 9, 27–39 (2006).
Underhill, D. M. & Ozinsky, A. Phagocytosis of microbes: complexity in action. Annu. Rev. Immunol. 20, 825–852 (2002).
Winter, C. et al. Lung-specific overexpression of CC chemokine ligand (CCL) 2 enhances the host defense to Streptococcus pneumoniae infection in mice: role of the CCL2–CCR2 axis. J. Immunol. 178, 5828–5838 (2007).
Bilyk, N. & Holt, P. G. Cytokine modulation of the immunosuppressive phenotype of pulmonary alveolar macrophages via regulation of nitric oxide production. Immunology 86, 231–237 (1995).
Landsman, L., Varol, C. & Jung, S. Distinct differentiation potential of blood monocyte subsets in the lung. J. Immunol. 178, 2000–2007 (2007).
Banham, A. H., Powrie, F. M. & Suri-Payer, E. FOXP3+ regulatory T cells: current controversies and future perspectives. Eur. J. Immunol. 36, 2832–2836 (2006).
Chen, C., Lee, W. H., Zhong, L. & Liu, C. P. Regulatory T cells can mediate their function through the stimulation of APCs to produce immunosuppressive nitric oxide. J. Immunol. 176, 3449–3460 (2006).
Huh, J. C. et al. Bidirectional interactions between antigen-bearing respiratory tract dendritic cells (DCs) and T cells precede the late phase reaction in experimental asthma: DC activation occurs in the airway mucosa but not in the lung parenchyma. J. Exp. Med. 198, 19–30 (2003).
Busse, W. W. & Lemanske, R. F. Asthma. N. Engl. J. Med. 344, 350–362 (2001).
Hartl, D. et al. Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma. J. Allergy Clin. Immunol. 119, 1258–1266 (2007).
Pasare, C. & Medzhitov, R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299, 1033–1036 (2003).
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M. & Murphy, K. M. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 24, 677–688 (2006).
Chen, Z. & O'Shea, J. J. Regulation of IL-17 production in human lymphocytes. Cytokine 2 November 2007 (doi:10.1016/j.cyto.2007.09.009).
Johnston, S. L. et al. The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. Am. J. Respir. Crit. Care Med. 154, 654–660 (1996).
Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A. & Sallusto, F. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nature Immunol. 8, 942–949 (2007).
Steinman, L. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell-mediated tissue damage. Nature Med. 13, 139–145 (2007). A recent review on the evolving T H 17-cell story, which is highly relevant to the pathogenesis of respiratory inflammatory diseases.
Liu, Y.-J. et al. TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu. Rev. Immunol. 25, 193–219 (2007). A definitive review on the role of epithelial-cell-derived thymic stromal lymphopoietin in programming DCs to drive the differentiation of specific subphenotype(s) of T H cells, in particular 'inflammatory' T H 2 cells.
Angkasekwinai, P. et al. Interleukin 25 promotes the initiation of proallergic type 2 responses. J. Exp. Med. 204, 1509–1517 (2007).
Bosco, A. et al. Identification of novel Th2-associated genes in T memory responses to allergens. J. Immunol. 176, 4766–4777 (2006).
Holt, P. G. et al. Drug development strategies for asthma: in search of a new paradigm. Nature Immunol. 5, 695–698 (2004).
Holt, P. G., Upham, J. W. & Sly, P. D. Contemporaneous maturation of immunological and respiratory functions during early childhood: Implications for development of asthma prevention strategies. J. Allergy Clin. Immunol. 116, 16–24 (2005).
Galli, S. J. et al. Mast Cells as “tunable” effector and immunoregulatory cells: recent advances. Annu. Rev. Immunol. 23, 749–786 (2005).
Galli, S. J., Nakae, S. & Tsai, M. Mast cells in the development of adaptive immune responses. Nature Immunol. 6, 135–142 (2005).
Malaviya, R., Ikeda, T., Ross, E. & Abraham, S. N. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-α. Nature 381, 77–80 (1996).
Nakae, S. et al. Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF. J. Immunol. 176, 2238–2248 (2006).
Lu, L. F. et al. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 442, 997–1002 (2006).
Suto, H. et al. Mast cell-associated TNF promotes dendritic cell migration. J. Immunol. 176, 4102–4112 (2006).
Byrne, P., McGuirk, P., Todryk, S. & Mills, K. H. G. Depletion of NK cells results in disseminating lethal infection with Bordetella pertussis associated with a reduction of antigen-specific Th1 and enhancement of Th2, but not Tr1 cells. Eur. J. Immunol. 34, 2579–2588 (2004).
Junqueira-Kipnis, A. P. et al. NK cells respond to pulmonary Infection with Mycobacterium tuberculosis, but play a minimal role in protection. J. Immunol. 171, 6039–6045 (2003).
Gazit, R. et al. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nature Immunol. 7, 517–523 (2006).
Haynes, L. M. et al. Involvement of Toll-like receptor 4 in innate immunity to respiratory syncytial virus. J. Virol. 75, 10730–10737 (2001).
Kronenberg, M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu. Rev. Immunol. 23, 877–900 (2005).
Godfrey, D. I. & Kronenberg, M. Going both ways: Immune regulation via CD1d-dependent NKT cells. J. Clin. Invest. 114, 1379–1388 (2004).
Tupin, E., Kinjo, Y. & Kronenberg, M. The unique role of natural killer T cells in the response to microorganisms. Nature Rev. Microbiol. 5, 405–417 (2007).
Meyer, E. H. et al. Glycolipid activation of invariant T cell receptor+ NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Proc. Natl Acad. Sci. USA 103, 2782–2787 (2006).
Akbari, O. et al. CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N. Engl. J. Med. 354, 1117–1129 (2006).
Vijayanand, P. et al. Invariant natural killer T cells in asthma and chronic obstructive pulmonary disease. N. Engl. J. Med. 356, 1410–1422 (2007).
Mulugeta, S. & Beers, M. F. Surfactant protein C: its unique properties and emerging immunomodulatory role in the lung. Microbes Infect. 8, 2317–2323 (2006).
Wright, J. R. Immunoregulatory functions of surfactant proteins. Nature Rev. Immunol. 5, 58–68 (2005).
Hawlisch, H. & Kohl, J. Complement and Toll-like receptors: key regulators of adaptive immune responses. Mol. Immunol. 43, 13–21 (2006).
Blasi, F., Tarsia, P. & Aliberti, S. Strategic targets of essential host-pathogen interactions. Respiration 72, 9–25 (2005).
Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389–395 (2002).
P.G.H. is supported by the National Health and Medical Research Foundation of Australia.
- Epithelial cells
Cells that line all tissues and act to protect them by regulating or resisting the passage of exogenous matter.
- Secretory goblet cells
Mucus-secreting cells within the airway epithelium.
- Plasmacytoid dendritic cells
(pDCs). A population of cells with a plasma-cell-like morphology that produce high levels of type I interferons after exposure to viruses. Human pDCs express high levels of CD123, the interleukin-3 receptor α-chain, and depend on interleukin-3 as a growth factor.
- Lamina propria
Loose connective tissue that is located immediately under the airway epithelium.
- Mast cells
A leukocyte population that secretes histamine and other inflammatory mediators on antibody crosslinking of its IgE receptors, and that is largely responsible for acute manifestations of the allergic response.
- Plasma cells
Antibody-secreting cells that are generated from antigen-specific B cells.
- Anergized cell
A cell that is characterized by its weak response to normal stimuli. An anergized T cell is unable to produce large amounts of interleukin-2 or proliferate vigorously when stimulated via CD3 or its T-cell receptor.
- Mucociliary elevator
Upward transport of mucus stream from the lungs by ciliated epithelial cells.
- Pattern-recognition receptors
(PRRs). Host receptors (such as Toll-like receptors) that are able to sense pathogen-associated molecular patterns and initiate signalling cascades (involving activation of nuclear factor-κB) that lead to an innate immune response.
Movement towards the epidermis.
- Protein-recall antigens
Antigens to which individuals or experimental animals have been previously sensitized.
- Inhalation tolerance
The development of immunological tolerance to repeatedly inhaled antigen.
About this article
Cite this article
Holt, P., Strickland, D., Wikström, M. et al. Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol 8, 142–152 (2008). https://doi.org/10.1038/nri2236
This article is cited by
Nature Reviews Rheumatology (2023)
Cellular & Molecular Immunology (2022)
Cell Death & Disease (2022)
Current Osteoporosis Reports (2022)
Reviews in Endocrine and Metabolic Disorders (2022)