Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes

Jakubzick, Claudia; Bogunovic, Milena; Bonito, Anthony J.; Kuan, Emma L.; Mérad, Miriam; Randolph, Gwendalyn J.

doi:10.1084/jem.20081430

Cited by 193 publications

(214 citation statements)

References 63 publications

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“…Experiments using either separation of parabionts or using genetic lineage tracing have reached different conclusions with regard to steady state DC turnover. In this regard, CD11b 1 cDC had a half-life of 15 days, whereas CD11b À CD103 1 cDC had a half-life of 30 days [7,12].…”

Section: Origin and Turnover Of Lung DC Subsetsmentioning

confidence: 96%

“…The studies employing the LysMCrexROSA26 stop-flox eGFP lineage tracing system show that 50-60% of each lung cDC population expresses eGFP, suggesting a monocytic intermediate stage [12]. For the CD11b 1 subset this is logical, as the CD11b 1 subset probably has a monocytic progenitor; however, these studies are hard to reconcile with a total absence of CD11b À cDC in Flt3L-deficient mice, which is suggestive of an absolute descent from pre-cDC progenitors [7].…”

Section: Origin and Turnover Of Lung DC Subsetsmentioning

confidence: 99%

“…Recent experiments have elegantly shed light on how lung DC subsets develop. Using adoptive transfer studies of monocytes in mice depleted of cDC, as well as using a genetic lineage tracing system employing lysozyme (Lys)MCre Â Stop/floxGFP as the reporter, it was shown that a large percentage of lung cDC do not derive from the Flt3 1 pre-cDC that seed the lymph nodes and spleen, but derive from circulating monocytes [12,19,20]. Contrasting these reports, two recent studies identified pre-cDC as the major contributing source for CD11b À CD103 1 lung cDC.…”

Section: Origin and Turnover Of Lung DC Subsetsmentioning

confidence: 99%

“…Although it was generally assumed that this process occurred constitutively, more recent studies have clearly demonstrated that some degree of danger recognition (e.g. provided by TLR stimulation on epithelial cells) is necessary for induction of DC migration [5,12]. In addition to the cell-mediated transport by DC, the barrier function made up of epithelial tight junctions could act as a molecular sieve that allows for some passage of small molecular weight antigens followed by entry into the afferent lymphatics.…”

Section: Migration To Mediastinal Lymph Nodesmentioning

confidence: 99%

“…In many mouse models of lung immunity, broncho-alveolar lavage is performed. The recovered lavage contains both CD11b 1 and CD11b À cDC, but it is unclear at present whether these derive from large airways or parenchyma [11,12]. Some DC also patrol the vessel wall of the pulmonary arterial vasculature, and these are mainly CX3CR1 1 CD11b 1 cells [13].…”

Section: Introducing Lung DC Heterogeneitymentioning

confidence: 99%

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Origin and functional specializations of DC subsets in the lung

2010

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Lung DC bridge innate and adaptive immunity, and depending on the context, induce Th1, Th2 or Th17 response, to optimally clear infections. Conversely, lung DC can also prevent overt and harmful immune responses to harmless inhaled antigens via induction of Treg cells or via induction of neutralizing mucosal IgA antibodies. Here, we propose that these functions are not the result of a single population of DC, and instead, subsets of DC perform specialized functions.

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Section: Origin and Turnover Of Lung DC Subsetsmentioning

confidence: 96%

Section: Origin and Turnover Of Lung DC Subsetsmentioning

confidence: 99%

Section: Origin and Turnover Of Lung DC Subsetsmentioning

confidence: 99%

Section: Migration To Mediastinal Lymph Nodesmentioning

confidence: 99%

Section: Introducing Lung DC Heterogeneitymentioning

confidence: 99%

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Origin and functional specializations of DC subsets in the lung

2010

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Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

272

258

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The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

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Induction of peripheral CD4⁺ T‐cell tolerance and CD8⁺ T‐cell cross‐tolerance by dendritic cells

Lutz

Kurts

2009

Eur J Immunol

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DC can present and cross-present self-antigens to autoreactive CD4 1 and CD8 1 T cells, respectively, and incapacitate them by inducing anergy, deletion or converting them into Treg. In this review, we summarize the recent progress in immune tolerance research, which has been achieved by employing antigen-and TCR-transgenic mice. We cover the numerous discoveries that have furthered our knowledge of the DC subsets and maturation pathways involved in tolerance; the signals, such as CD70, TGF-b, B7-H1/PD-L1, which dictate the decision between immunity and tolerance; and the in vivo role of DC in the maintenance of CD4 1 T-cell tolerance and CD8 1 T-cell cross-tolerance.Key words: Cross-presentation/priming . DC . T cells . Tolerance IntroductionTolerance of T cells to self-antigens is controlled at several levels. Thymic selection results in the release of high-affinity T cells specific for non-self-antigens, low-affinity T cells specific for self-antigens, and so-called natural Treg (nTreg) with an intermediate affinity to both self-and non-self-antigens into the circulation. In the steady-state, the self-reactive T cells may then interact with tissue cells or professional APC that present self-antigens both on MHC class I and II molecules. In the absence of infection or inflammation naive T cells will be either deleted, anergized, converted into adaptive CD4 1 CD251 Foxp3 1 Treg (aTreg) or develop into CD4 1 Foxp3 À IL-10-producing Treg (Tr1) [1,2]. The specific outcome is directed not only by the DC subset involved, the activation state of the DC, and the cytokine milieu of the anatomical location, but also by T-cell-intrinsic factors such as the TCR avidity. In addition, the nTreg, derived from the thymus, are continuously re-activated in LN to control self-reactive effector T cells [3]. The critical role for DC in the maintenance of CD4 1 T-cell self-tolerance has been summarized before [4] and has been further highlighted recently by conditional ablation of DC in mice [5][6][7]. Here, we review the recent findings relating to the mechanisms of DC presentation and cross-presentation of self-antigens in the maintenance of CD4 1 T-cell tolerance and CD8 1 T-cell cross-tolerance obtained using transgenic technology to visualize the otherwise very small repertoires of self-antigen-specific CD4 1 and CD8 1 T cells. This review will focus on the conventional (non-plasmacytoid) DC, referred to herein as DC.Antigen transport pathways for CD4 1 T-cell toleranceinduction in the draining LNThe immune system needs to be tolerized against self-antigens, including soluble and tissue-associated antigens, obtained for example from apoptotic cells [8]. LN-resident DC can capture soluble antigens from the reticular conduit system that originates from the upstream afferent lymphatics [9,10] Factors involved in the initiation, guidance and function of ssmDC In contrast to the factors guiding DC migration for T-cell priming, much less is known about the factors that control the mobilization of ssmDC. Only the requirement of CCR7 ...

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Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes

Cited by 193 publications

References 63 publications

Origin and functional specializations of DC subsets in the lung

Origin and functional specializations of DC subsets in the lung

Lymphatic Vessel Network Structure and Physiology

Induction of peripheral CD4⁺ T‐cell tolerance and CD8⁺ T‐cell cross‐tolerance by dendritic cells

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Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes

Cited by 193 publications

References 63 publications

Origin and functional specializations of DC subsets in the lung

Origin and functional specializations of DC subsets in the lung

Lymphatic Vessel Network Structure and Physiology

Induction of peripheral CD4+ T‐cell tolerance and CD8+ T‐cell cross‐tolerance by dendritic cells

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Product

Resources

About

Induction of peripheral CD4⁺ T‐cell tolerance and CD8⁺ T‐cell cross‐tolerance by dendritic cells