Abstract
Allergic asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness (AHR), chronic airway inflammation, and excessive T helper (Th) type 2 immune responses against harmless airborne allergens. Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system that act as a bridge between innate and adaptive immunity. Pertinent to allergic asthma, distinct DC subsets are known to play a central role in initiating and maintaining allergen driven Th2 immune responses in the airways. Nevertheless, seminal studies have demonstrated that DCs can also restrain excessive asthmatic responses and thus contribute to the resolution of allergic airway inflammation and the maintenance of pulmonary tolerance. Notably, the transfer of tolerogenic DCs in vivo suppresses Th2 allergic responses and protects or even reverses established allergic airway inflammation. Thus, the identification of novel DC subsets that possess immunoregulatory properties and can efficiently control aberrant asthmatic responses is critical for the re-establishment of tolerance and the amelioration of the asthmatic disease phenotype.
Highlights
Dendritic cells (DCs) denote the “professional” antigen presenting cells of our immune system and are responsible for the initiation and propagation of effective innate and subsequent adaptive immune responses [1]
In the first part of this review we briefly describe the immunopathophysiology of type II allergic asthma, as well as the role that DCs play in the instruction of allergen-specific T helper (Th)-cell mediated immune responses
Using unbiased single-cell RNA sequencing, Villani and colleagues provided a revised taxonomy pertinent to human blood DCs. They identified 6 DC populations (DC1-DC6): DC1 cluster is characterized as CD141/BDCA-3+CLEC9A+, DC2 and DC3 clusters represent subdivisions of CD1c/BDCA-1+ conventional DCs (cDCs), DC4 cluster is described as CD1c-CD141-CD11c+CD16+, DC5 is a cluster defined by the unique expression of the surface markers AXL and SIGLEC6, and DC6 is a cluster that corresponds to the interferon-producing CD123+CD303/BDCA-2+ plasmacytoid DCs (pDCs) [49,50]
Summary
Dendritic cells (DCs) denote the “professional” antigen presenting cells of our immune system and are responsible for the initiation and propagation of effective innate and subsequent adaptive immune responses [1]. Apart from the efficient activation of effector T cell-mediated immune responses, DCs are critically involved in the maintenance of immune homeostasis. A growing body of evidence suggests that the therapeutic transfer of DCs with immunoregulatory properties suppresses aberrant Th2 allergic responses and prevents, or even reverses, established allergic airway inflammation in experimental asthma [7,8,9]. In the first part of this review we briefly describe the immunopathophysiology of type II allergic asthma, as well as the role that DCs play in the instruction of allergen-specific Th-cell mediated immune responses. We provide an overview of our current understanding regarding DCs that acquire tolerogenic properties, representing critical controllers of excessive Th2-driven allergic airway inflammation in experimental asthma
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