Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10940987 | Immunobiology | 2015 | 8 Pages |
Abstract
Asthma is a heterogeneous chronic inflammatory disease of the airways, with reversible airflow limitations and airway remodeling. The classification of asthma phenotypes was initially based on different combinations of clinical symptoms, but they are now unfolding to link biology to phenotype. As such, patients can suffer from a predominant eosinophilic, neutrophilic or even mixed eosinophilic/neutrophilic inflammatory response. In adult asthma patients, eosinophilic inflammation is usually seen in mild-to-moderate disease and neutrophilic inflammation in more severe disease. The underlying T cell response is predominated by T helper (Th) 2, Th17, or a mixed Th2/Th17 cell immune response. Dendritic cells (DCs) are “professional” antigen presenting cells (APCs), since their principal function is to present antigens and induce a primary immune response in resting naive T cells. DCs also drive the differentiation into distinctive Th subsets. The expression of co-stimulatory molecules and cytokines by DCs and surrounding cells determines the outcome of Th cell differentiation. The nature of DC activation will determine the expression of specific co-stimulatory molecules and cytokines, specifically needed for induction of the different Th cell programs. Thus DC activation is crucial for the subsequent effector Th immune responses. In this review, we will discuss underlying mechanisms that initiate DC activation in favor of Th2 differentiation versus Th1/Th17 and Th17 differentiation in the development of mild versus moderate to severe asthma.
Keywords
T helper 17 cellsTLRILCMD2PPRGM-CSFBcl-6CLRATSTregSAANLRTNFAIP3Airway hyper responsivenessRORγtHDMTSLPMLNT helperTFHnucleotide oligomerization domainIRFRLRRIGDC-SIGNPlasmacytoid DCconventional DCAHRNODLPSGATA-binding protein 3FOXP3GATA-3CDCPDCTCrDAMPT helper 2 cellsDEPPAMPBALAPCAsthmaSTATEosinophilsdamage associated molecular patternAmerican Thoracic SocietyT-betToll-like receptordiesel exhaust particleserum amyloid ARegulatory T cellDendritic cellinnate lymphoid cellDendritic cellsantigen presenting cellGlobal Initiative for Asthmainterferon regulatory factorgranulocyte–macrophage colony-stimulating factorT-box transcription factor bronchoalveolar lavageB-cell lymphomaThymic stromal lymphopoietinlipopolysaccharideSignal transducer and activator of transcriptionComplementgenome wide association studiesGWASNeutrophilspathogen associated molecular patternAntigenforkhead box protein 3Single nucleotide polymorphismSNPretinoic acid-inducible geneHouse dust miteMediastinal lymph nodeT cell receptorpathogen recognition receptorC-type lectin receptorMannose receptorGINA
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Authors
Heleen Vroman, Bernt van den Blink, Mirjam Kool,