GM-CSF and dendritic cells in allergic airway inflammation: basic mechanisms and prospects for therapeutic intervention.
The interaction between dendritic cells (DC) and naïve T cells is the first step in the evolution of an immune response, either tolerogenic or inflammatory. Therefore, the status of DC residing at mucosal sites, such as the airway, has a definitive impact on the character of the ensuing immune response. In the absence of pathogenic stimulation, DC serve to regulate immunological homeostasis in the lung; the generation of Th2-associated (allergic) inflammatory responses, which are directed at presumably innocuous antigens, represent a deviation from normal DC function. The dysregulation of DC phenotype leading to the development of allergy might be programmed by genetic pedigree, or might be induced by factors released in the airway. One potential candidate, GM-CSF, is abundant in the allergic airway and can condition DC to propagate Th2 responses. Moreover, that allergens, alone or in combination with other factors, can spontaneously induce GM-CSF production in the airway thus present a compelling etiological argument for the role of GM-CSF in allergic sensitization. The interplay between DC and mediators present in the allergic airway is likely critical to the establishment of allergic airway inflammation. Understanding these interactions may, therefore, afford insight into prospective therapeutic interventions to circumvent, and even reverse the allergic diathesis.
Gajewska
Beata U
BU
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
Wiley
Ryan E
RE
Jordana
Manel
M
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D003713:Dendritic Cells / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D012137:Respiratory System / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology
D018927:Anti-Asthmatic Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor