Origin of dendritic cells in peripheral lymphoid organs of mice

Liu, Kang; Waskow, Claudia; Liu, Xiangtao; Yao, Kai-Hui; Hoh, Josephine; Nussenzweig, Michel C.

doi:10.1038/ni1462

Cited by 400 publications

(485 citation statements)

References 47 publications

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“…Thus, the degree of cellular Xux through the dermis in the steady-state greatly exceeds that of the epidermis. This is consistent with studies of DC lifespan, which report a complete replacement of DDCs by BM-derived precursors within 2 weeks (Iijima et al 2007;Kamath et al 2002;Liu et al 2007), while only 20-60% of LCs turn over in this same period (Henri et al 2001).…”

Section: Lcs and Ddcs In The Skin In Vivo: Lessons From Confocal Micrsupporting

confidence: 90%

“…In contrast to LCs, DDCs display an amoeboid morphology (Ng et al 2008a), more characteristic of a migratory cell (Gunzer et al 2000). In the mouse, DDCs are replaced every 10-15 days by bone marrow (BM)-derived precursors (Iijima et al 2007;Kamath et al 2002;Liu et al 2007). Furthermore, DDCs mobilize rapidly in response to inXammation, arriving in draining LNs within »12 h of stimulation, and peaking at 1-2 days (Kissenpfennig et al 2005;Shklovskaya et al 2008).…”

Section: Dendritic Cells In the Skinmentioning

confidence: 99%

“…This raises the question of what drives LC and DDC emigration from the skin during the steady-state. Ample experimental evidence shows that both LCs and DDCs migrate continuously from the skin to the draining LNs under non-inXammatory conditions, as shown by BrdU uptake (Kamath et al 2002), BM chimeric experiments (Merad et al 2002), and studies utilizing parabiotic mice (Liu et al 2007). While the precise mechanisms underlying this phenomenon remain to be determined, a recent study by Mellman and colleagues has described a distinct pathway of DC maturation that can occur in the absence of inXammatory signals (Jiang et al 2007).…”

Section: Dendritic Cell Maturationmentioning

confidence: 99%

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Visualizing dendritic cell migration within the skin

Roediger

Smith

et al. 2008

Histochem Cell Biol

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Dendritic cells (DCs) within the skin are a heterogeneous population of cells, including Langerhans cells of the epidermis and at least three subsets of dermal DCs. Collectively, these DCs play important roles in the initiation of adaptive immune responses following antigen challenge of the skin as well as being mediators of tolerance to self-antigen. A key functional aspect of cutaneous DCs is their migration both within the skin and into lymphatic vessels, resulting in their emigration to draining lymph nodes. Here, we discuss our current understanding of the requirements for successful DC migration in and from the skin, and introduce some of the microscopic techniques developed in our laboratory to facilitate a better understanding of this process. In particular, we detail our current use of multi-photon excitation (MPE) microscopy of murine skin to dissect the migratory behavior of DCs in vivo.

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Section: Lcs and Ddcs In The Skin In Vivo: Lessons From Confocal Micrsupporting

confidence: 90%

Section: Dendritic Cells In the Skinmentioning

confidence: 99%

Section: Dendritic Cell Maturationmentioning

confidence: 99%

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Visualizing dendritic cell migration within the skin

Roediger

Smith

et al. 2008

Histochem Cell Biol

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“…cDCs have a short half-life and are constantly replaced from bone marrow precursors generated in a FMS-like tyrosine kinase 3 ligand (Flt3L)-dependent manner. 7 At the molecular level, the generation of cDCs is controlled by transcription factor Zbtb46 (zinc finger and BTB domain containing 46) 8,9 and also by the transcription factors B-cell lymphoma 6 proteinv-rel avian reticuloendotheliosis viral oncogene homolog B and IRF4. [10][11][12][13] Two major subsets of cDCs have been identified: cluster of differentiation 8a þ (CD8a þ ) cDCs and CD11b þ cDCs.…”

Section: Classes Of Dcsmentioning

confidence: 99%

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

2014

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Dendritic cells (DCs) are professional antigen-presenting cells that control the generation of adaptive immunity. Consequently, DCs have a central role in the induction of protective immunity to pathogens and also in the pathogenic immune response responsible for the development and progression of autoimmune disorders. Thus the study of the molecular pathways that control DC development and function is likely to result in new strategies for the therapeutic manipulation of the immune response. In this review, we discuss the role and therapeutic value of DCs in autoimmune diseases, with a special focus on multiple sclerosis. Cell Death and Differentiation (2015) 22, 215-224; doi:10.1038/cdd.2014; published online 29 August 2014 FactsDendritic cells (DCs) control central and peripheral tolerance through their effects on effector and regulatory T cells. Specific signaling pathways regulate the ability of different DC populations to promote effector and regulatory T-cell responses. Abnormalities in DC numbers, recruitment and function contribute to the pathology of multiple sclerosis (MS) and can be partially overcome by the use of disease-modifying therapies and the targeting of specific molecular pathways. Nanotechnology provides new tools for the modulation of DC activity in vivo and the therapeutic induction of antigenspecific tolerance in immune-mediated disorders. Open QuestionsAlthough DC populations that promote the development of forkhead box P3-positive (FoxP3 þ ) regulatory T cells (Tregs) have been identified, it is not yet clear whether these populations constitute separate tolerogenic DC lineages or represent alternative activation or maturation states of other DC populations. What are the different molecular pathways that control the DC's ability to prime effector or tolerogenic T-cell responses?There is an unmet clinical need for the development of methods for the efficient and consistent generation of tolerogenic DCs in vitro and in vivo that can be implemented in large-scale clinical setups.Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that control the activation and polarization of T cells into specific lineages and, consequently, the generation of antigen-specific antibody and T-cell responses. 1 In the context of an infectious challenge, the induction of pathogenspecific immune responses provides protective immunity to fight the infection. However, in the context of autoimmune diseases DCs regulate the balance between pathogenic and regulatory immune mechanisms, controlling disease onset and progression. Thus, DCs have a central role in the control of the adaptive immune response to pathogens and selftissues and therefore constitute potential targets for the therapeutic modulation of the immune response. In this review, we discus the role of DCs in autoimmune diseases, with a special emphasis on their role in the modulation of central nervous system (CNS) inflammation in MS. Received 12.6.14; accepted 23.6.14; Edited by H-U Simon; published online 29.8.14 Abbreviations: A...

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“…Furthermore, some T cells may gain immediate access to APC whereas others make contact later [20]. Diversity in both quality and duration of the stimulatory signal is caused by progressive maturation of APC, their limited lifespan, and dilution of captured antigen by cell division [21]. Exactly these asynchronous and non-uniform priming conditions may result in In view of this notion, we chose to study the impact of activation signals on effector cell differentiation and memory formation by means of an experimental system that circumvents the heterogeneity of the in vivo priming setting.…”

Section: Introductionmentioning

confidence: 99%

Development of CTL memory despite arrested clonal expansion

Stipdonk¹,

Sluijter²,

Han³

et al. 2008

Eur J Immunol

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Activation of a cytotoxic T lymphocyte (CTL) response in an antigen-exposed lymph node involves a great diversity of encounters between naive CTL and APC that differ in both duration and quality. This broad spectrum of priming events instigates a complex blend of CTL developmental pathways. Using an experimental system that allows tight control over CTL priming, we have singled out defined priming events and analyzed the impact of the resulting instructional program on the effector and memory phases of the CTL response. As expected, prolonged antigenic stimulation induces potent CTL expansion, effector function and CTL memory. In contrast, CTL that have received suboptimal stimulation fail to undergo extensive expansion. Nevertheless these arrested CTL persist long term and acquire memory function. Thus, our data demonstrate that CTL memory can develop as a result of a suboptimal stimulation that causes arrested clonal expansion. Key words: CD8 T cells Á Cell differentiation Á Cellular proliferation Á Memory cells IntroductionT cells protect the health of an organism by mounting a wellorchestrated immune response consisting of proliferation, effector cell differentiation, contraction and memory formation. These aspects of the T cell response are programmed during the initial contact of naive T cells with antigen-presenting cells (APC) [1][2][3][4]. The strength of the signal that is delivered during primary stimulation determines the quality of the T cell differentiation program [5,6]. The interrelationship between the T cell types that represent the different stages of the immune response, the naive T cells, effector T cells and memory T cells, is still a matter of debate. Some studies support a linear differentiation model wherein naive T cells first develop into effector cells and thereafter into memory cells [7][8][9]. Other studies suggest (partially) parallel pathways of effector and memory T cell generation [10, 11].As a consequence of the primary T cell response, different subsets of memory T cells can emerge, in particular the central memory (Tcm) and effector memory (Tem) T cells. Although the exact phenotypic definitions of the two subsets differ slightly between mouse and human T cells and among different research groups, it is generally accepted that Tcm cells express CD62L and therefore preferentially localize in lymphoid tissues, whereas Tem cells lack these features and therefore mainly reside in the blood and non-lymphoid tissues (reviewed in [12,13]). The two memory subsets also complement each other functionally, in that Tem cells exhibit immediate effector function while Tcm cells cause expansion of responding cells through extensive cell division. The lineage relationship between the subsets of memory cells is still unclear, calling for further study on the factors deciding between the formation of Tcm versus Tem cells [14][15][16][17]. A recent study has shed some light on this issue by showing that high T cell precursor frequencies favor Tcm cell formation while low precursor frequencies p...

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Origin of dendritic cells in peripheral lymphoid organs of mice

Cited by 400 publications

References 47 publications

Visualizing dendritic cell migration within the skin

Visualizing dendritic cell migration within the skin

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

Development of CTL memory despite arrested clonal expansion

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