Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells

Haniffa, Muzlifah; Shin, Amanda; Bigley, Venetia; McGovern, Naomi; Teo, Pearline; See, Peter; Wasan, Pavandip Singh; Wang, Xiao Nong; Malinarich, Frano; Malleret, Benoît; Larbi, Anis; Tan, Pearlie W.W.; Zhao, Helen; Poidinger, Michael; Pagan, Sarah; Cookson, Sharon; Dickinson, Rachel; Dimmick, Ian; Jarrett, Ruth F.; Rénia, Laurent; Tam, John S.; Song, Colin; Connolly, John E.; Chan, Jerry Kok Yen; Gehring, Adam J.; Bertoletti, Antonio; Collin, Matthew; Ginhoux, Florent

doi:10.1016/j.immuni.2012.04.012

Cited by 637 publications

(922 citation statements)

References 55 publications

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“…In light of these results, some investigators predicted that a CD11c hi CD1a + CD141 hi CLEC9A + TLR3 hi DC subtype should exist in nonlymphoid human tissues (28). In 2012, Haniffa et al (29) succeeded in identifying this population in human skin, skin-draining lymph nodes, liver, and lung. Through an extensive and detailed phenotypic identification of diverse DC subsets, the investigators demonstrated that human skin CD141 hi DCs are closely related to human blood CD141 + DCs and to mice crosspresenting cells (lymphoid CD8a + DCs and CD103 + migratory DCs) (29).…”

Section: Endritic Cells (Dcs) Belong To the Family Of Professionalmentioning

confidence: 99%

“…In 2012, Haniffa et al (29) succeeded in identifying this population in human skin, skin-draining lymph nodes, liver, and lung. Through an extensive and detailed phenotypic identification of diverse DC subsets, the investigators demonstrated that human skin CD141 hi DCs are closely related to human blood CD141 + DCs and to mice crosspresenting cells (lymphoid CD8a + DCs and CD103 + migratory DCs) (29). Such a cross-presenting DC subtype in human epithelia was identified as one of the main targets for clinical studies aimed at inducing efficient CD8 + T cell responses against intracellular pathogens and tumors (30).…”

Section: Endritic Cells (Dcs) Belong To the Family Of Professionalmentioning

confidence: 99%

“…4A). Although murine CD8 + DCs do not express TLR7 (48), TLR3 is considered a signature marker for cross-presenting DCs, murine CD103 + tissue and CD8 + lymphoid DCs, and the human CD141 + DC lineage (29). Consequently, we analyzed whether trout skin sorted CD8 + dendritic-like cells responded to stimulation with poly I:C, a known ligand for teleost TLR3 and TLR22 (49), or bacterial LPS, as an irrelevant TLR3 ligand.…”

Section: Response Through Tlrsmentioning

confidence: 99%

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Identification of Teleost Skin CD8α+ Dendritic-like Cells, Representing a Potential Common Ancestor for Mammalian Cross-Presenting Dendritic Cells

Granja¹,

Leal²,

Pignatelli³

et al. 2015

The Journal of Immunology

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Although fish constitute the most ancient animal group in which an acquired immune system is present, the presence of dendritic cells (DCs) in teleosts has been addressed only briefly, and the identification of a specific DC subset in teleosts remained elusive because of the lack of specific Abs. In mice, DCs expressing CD8α+ in lymphoid tissues have the capacity to cross-present extracellular Ags to T cells through MHC I, similarly to tissue-derived CD103+ DCs and the human CD141+ DC population. In the current study, we identified a large and highly complex subpopulation of leukocytes coexpressing MHC class II and CD8α. This CD8α+ MHC II+ DC-like subpopulation constituted ∼1.2% of the total leukocyte population in the skin, showing phenotypical and functional characteristics of semimature DCs that seem to locally regulate mucosal immunity and tolerance in a species lacking lymph nodes. Furthermore, we identified trout homologs for CD141 and CD103 and demonstrated that, in trout, this skin CD8+ DC-like subpopulation expresses both markers. To our knowledge, these results provide the first evidence of a specific DC-like subtype in nonimmune tissue in teleosts and support the hypothesis of a common origin for all mammalian cross-presenting DCs.

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Section: Endritic Cells (Dcs) Belong To the Family Of Professionalmentioning

confidence: 99%

Section: Endritic Cells (Dcs) Belong To the Family Of Professionalmentioning

confidence: 99%

Section: Response Through Tlrsmentioning

confidence: 99%

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Identification of Teleost Skin CD8α+ Dendritic-like Cells, Representing a Potential Common Ancestor for Mammalian Cross-Presenting Dendritic Cells

Granja¹,

Leal²,

Pignatelli³

et al. 2015

The Journal of Immunology

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“…A specific subset of BDCA3 bright /CLEC9a + /Sirpa 2 DCs has recently been described in different human tissues (10)(11)(12)32). These DCs resemble murine CD8a + DCs in their ability to crosspresent exogenous Ags.…”

Section: Two Distinct Subsets Of Dcs Are Present In Human Afferent Lymentioning

confidence: 99%

“…In contrast, in the past few years, different subsets of DCs have been identified in human blood (BDCA1 + and BDCA3 + ) (7)(8)(9)(10) and skin (1,(11)(12)(13)(14)(15). In addition, we have lately gained access to a comprehensive depiction of DCs harbored in human lymph nodes (16)(17)(18), obtaining valuable information on migratory DC subtypes.…”

mentioning

confidence: 99%

Characterization of Human Afferent Lymph Dendritic Cells from Seroma Fluids

Morandi

Bonaccorsi

Mesiti

et al. 2013

The Journal of Immunology

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Dendritic cells (DCs) migrate from peripheral tissues to secondary lymphoid organs (SLOs) through the afferent lymph. Owing to limitations in investigating human lymph, DCs flowing in afferent lymph have not been properly characterized in humans until now. In this study, DCs present in seroma, an accrual of human afferent lymph occurring after lymph node surgical dissection, were isolated and analyzed in detail. Two main DC subsets were identified in seroma that corresponded to the migratory DC subsets present in lymph nodes, that is, CD14+ and CD1a+. The latter also included CD1abright Langerhans cells. The two DC subsets appeared to share the same monocytic precursor and to be developmentally related; both of them spontaneously released high levels of TGF-β and displayed similar T cell–activating and –polarizing properties. In contrast, they differed in the expression of surface molecules, including TLRs; in their phagocytic activity; and in the expression of proteins involved in Ag processing and presentation. It is worth noting that although both subsets were detected in seroma in the postsurgical inflammatory phase, only CD1a+ DCs migrated via afferent lymph under steady-state conditions. In conclusion, the high numbers of DCs contained in seroma fluids allowed a proper characterization of human DCs migrating via afferent lymph, revealing a continuous stream of DCs from peripheral regions toward SLOs under normal conditions. Moreover, we showed that, in inflammatory conditions, distinct subsets of DCs can migrate to SLOs via afferent lymph.

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Dendritic Cells

See

Ginhoux

2015

Encyclopedia of Life Sciences

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Dendritic cells (DCs) are distributed in almost all tissues body, acting as sentinels of the immune system. They serve as specialised pathogen‐sensing and antigen‐presenting cells that initiate and regulate the immune response. DCs are derived from unique progenitors present in the bone marrow, which seed the tissues where they differentiate into mature DCs. Transcriptomic, phenotypic and functional analyses indicate that human and murine DCs can be divided into three subsets: two subsets of conventional DCs (cDC) named cDC1 and cDC2, and a third lineage of plasmacytoid DCs (pDCs). Each subset is unique and has distinct functional specialisations to control specific T‐cell responses. DCs form a complex cellular network capable of integrating multiple environmental signals and can induce either immunity or tolerance. As a consequence, DCs are suitable candidates for therapeutic intervention in immune‐mediated conditions. Key Concepts Dendritic cells are a heterogeneous group of specialised pathogen‐sensing and antigen‐presenting cells. They are distributed in almost all tissues and organs, and act as sentinels of the immune system. They are derived from DC‐restricted progenitors present in the bone marrow and arise from a dedicated lineage. They can be grouped into three subsets based on ontogeny and transcription factor dependency: two lineages of conventional DCs named cDC1 and cDC2, as well as a third lineage of plasmacytoid DCs (pDCs). Each subset is unique and has distinct functional specialisations. The cDC1 subset is efficient at cross‐presentation, and elicits Th1 responses. The cDC2 subset is capable of eliciting Th2 and Th17 responses. pDCs produce large amounts of type I interferons to combat viral infections.

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Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells

Cited by 637 publications

References 55 publications

Identification of Teleost Skin CD8α+ Dendritic-like Cells, Representing a Potential Common Ancestor for Mammalian Cross-Presenting Dendritic Cells

Identification of Teleost Skin CD8α+ Dendritic-like Cells, Representing a Potential Common Ancestor for Mammalian Cross-Presenting Dendritic Cells

Characterization of Human Afferent Lymph Dendritic Cells from Seroma Fluids

Dendritic Cells

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