Biology of Lung Dendritic Cells at the Origin of Asthma

Abstract

Dendritic cells (DCs) initiate and maintain adaptive T helper 2 (Th2) cell responses to inhaled allergens in asthma. Various functions like antigen uptake, migration to the draining LNs, and induction of tolerance and adaptive immunity are not equally shared by all subsets of DCs, adding considerable complexity to understanding the immunology of allergic sensitization. Whereas the epithelium was initially considered solely as a physical barrier, it is now seen as a central player in controlling the function of lung DCs through release of Th2 cell-promoting cytokines. Although DCs are sufficient and necessary for induction of Th2 cell responses to many antigens, some allergens might require antigen presentation by basophils. Clinically relevant allergens, as well as environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells, basophils, and DCs. This review summarizes the recent progress on our understanding how DCs control Th2 cell immunity in the lung.

Signal Relay by CC Chemokine Receptor 2 (CCR2) and Formylpeptide Receptor 2 (Fpr2) in the Recruitment of Monocyte-derived Dendritic Cells in Allergic Airway Inflammation

“…2 play critical roles in airway inflammatory responses (1,2). Under inflammatory conditions, such as viral infection, allergen challenge, or endotoxin inhalation, CD11b ϩ monocyte-derived DCs are rapidly recruited from the circulation.…”

GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

“…Lung-resident dendritic cells (DCs) play a critical role in asthma by orchestrating the priming and polarization of CD4 + T cells (20)(21)(22)(23). Although lung DCs have been shown to control the induction of allergic responses to the dust mite (24,25), there has been considerable debate about which lung DC subset is responsible for priming Th2 CD4 + T cells. Lung DCs, as well as other nonlymphoid tissue DC populations, are distinguished by mutually exclusive surface expression of the integrins CD103 and CD11b at steady state (26).…”

Nonhematopoietic Cells Are Key Players in Innate Control of Bacterial Airway Infection

“…Mucosal tissues have adapted to confront this assault by various means: during steady-state conditions (i.e., in absence of pathogenic microbes), epithelial cells, together with their mucous lining and the constitutive expression of antimicrobial substances, represent a physical and biological barrier for commensal microorganisms. The innate defense system in the lung consists of: 1) airway epithelial cells (AECs) and their products (the airway surface liquid, antimicrobial substances, cytokines, and chemokines); 2) alveolar macrophages (AMs), which are strategically positioned at the luminal surface of the epithelial lining being responsible for efficient phagocytic uptake and clearance of microbes; and 3) dendritic cells (DCs), which were shown to capture particulate Ags through transepithelial luminal dendrites (1)(2)(3).…”