Dendritic cell subsets and immune regulation in the lung

Heer, Hendrik Jan de; Hammad, Hamida; Kool, Mirjam; Lambrecht, Bart N.

doi:10.1016/j.smim.2005.05.002

Cited by 121 publications

(99 citation statements)

References 100 publications

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“…In their immature state, they take up antigen, and in the context of a danger signal (PAMP) migrate to the draining lymph node, where they become fully mature and provide costimulatory molecules and cytokine signals for initiating and polarizing the T helper response. To further complicate matters, at least two different subsets of DCs have been shown to be important in respiratory tract responses to antigens, namely myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) (28,29). Myeloid DCs produce little IL-12, a prototype Th1-skewing cytokine, yet secrete the Th2-prone cytokine IL-6, while pDCs predominantly secrete IFN-␣, but also produce IL-12.…”

Section: Role Of C5/c5a In Regulating Adaptive Immune Response To Allmentioning

confidence: 99%

“…Myeloid DCs produce little IL-12, a prototype Th1-skewing cytokine, yet secrete the Th2-prone cytokine IL-6, while pDCs predominantly secrete IFN-␣, but also produce IL-12. De Heer and colleagues have elegantly shown that myeloid DCs appear to drive Th2 sensitization to inhaled antigens, while pDCs mediate the development of tolerance to inhaled antigens (28). Interestingly, a deficiency in C5, either due to a genetic deletion or to pharmacologic blockade of the C5aR during priming to inhaled OVA or HDM, leads to an early and persistent shift of the proportion of the mDC to pDCs in the lungs and to the development of an effector Th2 response (20).…”

Section: Role Of C5/c5a In Regulating Adaptive Immune Response To Allmentioning

confidence: 99%

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Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

Wills‐Karp

2007

Proceedings of the American Thoracic Society

104

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Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, is no exception. The emerging paradigm is that C3a production at the airway surface serves as a common pathway for the induction of Th2-mediated inflammatory responses to a variety of environmental triggers of asthma (i.e., allergens, pollutants, viral infections, cigarette smoke). In contrast, C5a plays a dual immunoregulatory role by protecting against the initial development of a Th2-polarized adaptive immune response via its ability to induce tolerogenic dendritic cell subsets. On the other hand, C5a drives type 2-mediated inflammatory responses once inflammation ensues. Thus, alterations in the balance of generation of the various components of the complement pathway either due to environmental exposure changes or genetic alterations in genes of the complement cascade may underlie the recent rise in asthma prevalence in westernized countries.

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Section: Role Of C5/c5a In Regulating Adaptive Immune Response To Allmentioning

confidence: 99%

Section: Role Of C5/c5a In Regulating Adaptive Immune Response To Allmentioning

confidence: 99%

Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

Wills‐Karp

2007

Proceedings of the American Thoracic Society

104

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“…Airway mucosal DC are thought to derive from myeloid precursors (Lambrecht et al, 2000a,b). After exposure to allergen they express high levels of MHC class II and CD11c (Wikstrom & Stumbles, 2007) and are functionally immature as shown by low expression of costimulatory molecules CD40, CD80 and CD86 (Stumbles et al, 1998;Huh et al, 2003;de Heer et al, 2005;van Rijt et al, 2005). They are able to capture antigen rapidly in the main conducting airways (Lambrecht, 2001;Vermaelen et al, 2001;von Garnier et al, 2007).…”

Section: Distribution and Function Of Respiratory Tract Dendritic Cellsmentioning

confidence: 99%

The role of dendritic cells and regulatory T cells in the regulation of allergic asthma

Burchell

Strickland

Stumbles

2010

Pharmacology & Therapeutics

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Airways hyperresponsiveness (AHR) is one of the major clinical features of allergic airways disease including allergic asthma, however the immunological mechanisms leading to the induction and regulation of this disorder are not fully understood. In this review we will summarise the evidence of a number of studies, principally in murine models of AHR, suggesting a central role for respiratory tract dendritic cells (RTDC) in the induction of AHR through the generation of lung-homing, allergen-specific effector T cells. We will also summarise the evidence supporting a role for regulatory T cells in the attenuation of AHR and will propose that, as a counterpoint to their capacity to induce AHR, RTDC may also play a role in the attenuation of AHR through the generation of regulatory T cells (Treg). A better understanding of the relationship between the physiological and immunological responses to allergen-induced AHR attenuation, and particularly the role of RTDC and Treg in this process, will be essential for the development of new treatments and therapies.

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“…A blood–air barrier formed from a single fused basal lamina of alveolar cells and endothelium, hosting a plethora of cells like dendritic cells (DCs), mast cells, and lymphocytes with secretory immunoglobulin. They not only play a role in antigen recognition and allergic reactions [4,5], but wandering alveolar macrophages that engulf foreign substances can be another barrier for carrier and macromolecule delivery. The absorption of deposited particles in the alveolar barrier is through either receptor-mediated transcytosis, paracellular passive transport via tight junctions, endocytosis, and engulfed by macrophages [6].…”

Section: Introductionmentioning

confidence: 99%

“…The therapeutic agent, after recognition as ‘foreign,’ is internalized, processed, and presented by antigen-presenting cells (APC), resulting in CD4 T-cell responses and the elevation in antibody titer. This immunogenic reaction can be used to our advantage and is sometimes targeted as in vaccine prophylaxis and therapeutics [5]. …”

Section: Introductionmentioning

confidence: 99%

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

Osman

Kaneko

Carini

et al. 2018

Expert Opinion on Drug Delivery

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Introduction: Macromolecules with unique effects and potency are increasingly being considered for application in lung pathologies. Numerous delivery strategies for these macromolecules through the lung have been investigated to improve the targeting and overall efficacy.Areas covered: Targeting approaches from delivery devices, formulation strategies and specific targets are discussed.Expert opinion: Although macromolecules are a heterogeneous group of molecules, a number of strategies have been investigated at the macro, micro, and nanoscopic scale for the delivery of macromolecules to specific sites and cells of lung tissues. Targeted approaches are already in use at the macroscopic scale through inhalation devices and formulations, but targeting strategies at the micro and nanoscopic scale are still in the laboratory stage. The combination of controlling lung deposition and targeting after deposition, through a combination of targeting strategies could be the future direction for the treatment of lung pathologies through the pulmonary route.

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Dendritic cell subsets and immune regulation in the lung

Cited by 121 publications

References 100 publications

Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

The role of dendritic cells and regulatory T cells in the regulation of allergic asthma

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

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