Dermal-resident CD14+ cells differentiate into Langerhans cells

Larregina, Adriana T.; Morelli, Adrián E.; Spencer, Lori; Logar, Alison J.; Watkins, Simon C.; Thomson, Angus W.; Falo, Louis D.

doi:10.1038/ni731

Cited by 197 publications

(212 citation statements)

References 37 publications

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“…Another provocative study supports the view that during inflammation, LCs are replaced by circulating bone marrow precursors or monocytes, via inflammatory chemokine receptors, while during steady state, LCs are long-lived and either are replaced by a skin resident precursor or proliferate locally to sustain the low number of migratory LCs (10,20,24). Whether this model turns out to be true in vivo remains to be shown, and how it might relate to other DC subsets is unknown.…”

Section: Discussionmentioning

confidence: 57%

“…Similar to T cells (41), the process of APC precursor recruitment toward peripheral tissues during homeostasis remains largely unknown. Most of the studies so far have concentrated on the recruitment of LCs into the epidermis (5,8,20,52). The chemokine CCL20, the single ligand for CCR6, was originally proposed to regulate LC recruitment during steady state (5); however, the expression of CCL20 in uninflamed skin could not be confirmed by others (8,13).…”

Section: Discussionmentioning

confidence: 95%

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Murine CXCL14 Is Dispensable for Dendritic Cell Function and Localization within Peripheral Tissues

Meuter

Schaerli

Roos

et al. 2007

Molecular and Cellular Biology

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Dendritic cells (DCs) have long been recognized as key regulators of immune responses. However, the process of their recruitment to peripheral tissues and turnover during homeostasis remains largely unknown. The chemokine CXCL14 (BRAK) is constitutively expressed in skin and other epithelial tissues. Recently, the human chemokine was proposed to play a role in the homeostatic recruitment of macrophage and/or DC precursors toward the periphery, such as skin. Although so far no physiological function could be demonstrated for the murine CXCL14, it shows a remarkable homology to the human chemokine. In order to elucidate the in vivo role of CXCL14, we generated a mouse defective for this chemokine. We studied various components of the immune system with emphasis on monocytes/macrophages and DC/Langerhans cell (LC) populations in different tissues during steady state but did not find a significant difference between knockout (CXCL14 ؊/؊ ) and control mice. Functionally, LCs were able to become activated, to migrate out of skin, and to elicit a delayed type of hypersensitivity reaction. Overall, our data indicate that murine CXCL14 is dispensable for the homeostatic recruitment of antigen-presenting cells toward the periphery and for LC functionality.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 95%

Murine CXCL14 Is Dispensable for Dendritic Cell Function and Localization within Peripheral Tissues

Meuter

Schaerli

Roos

et al. 2007

Molecular and Cellular Biology

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“…Although blood-borne LC precursors have not been clearly identified, different studies suggest that monocytes 23 , circulating MHC class II − (I-A b− )CD11c + cells 24 , dermal CD14 + cells 25 and CD34 + cell-derived CD1a + cells 26 may give rise to LCs. Monocytes express a variety of chemokine receptors, including CCR1, CCR2, CCR5 and CXCR4, whereas dermal CD14 + cells and CD34 + cell-derived CD1a + cells do not express CCR1, CCR2 or CCR5 but express CCR6 25,26 . We found that freshly isolated LCs as well as circulating I-A b− CD11c + cells expressed CCR2 (Fig.…”

Section: Role Of Ccr2 In the Recruitment Of Lc Precursorsmentioning

confidence: 99%

Langerhans cells renew in the skin throughout life under steady-state conditions

et al. 2002

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Langerhans cells (LCs) are bone marrow (BM)-derived epidermal dendritic cells (DCs) that represent a critical immunologic barrier to the external environment, but little is known about their life cycle. Here, we show that in lethally irradiated mice that had received BM transplants, LCs of host origin remained for at least 18 months, whereas DCs in other organs were almost completely replaced by donor cells within 2 months. In parabiotic mice with separate organs, but a shared blood circulation, there was no mixing of LCs. However, in skin exposed to ultraviolet light, LCs rapidly disappeared and were replaced by circulating LC precursors within 2 weeks. The recruitment of new LCs was dependent on their expression of the CCR2 chemokine receptor and on the secretion of CCR2-binding chemokines by inflamed skin. These data indicate that under steady-state conditions, LCs are maintained locally, but inflammatory changes in the skin result in their replacement by blood-borne LC progenitors.Langerhans cells (LCs) are members of a family of highly specialized antigen-presenting cells called dendritic cells (DCs) 1-3 . They are typically localized in the basal and suprabasal layers of the epidermis and represent the principal hematopoietic barrier to the external environment. LCs are well equipped to ingest foreign antigens that breach the skin. Upon activation, LCs increase their expression of major histocompatibility complex (MHC) class II and costimulatory molecules and migrate to the T cell areas of regional lymph nodes (LNs) where they initiate a systemic immune response by presenting processed antigens to T cells 1,4 .Given the importance of LCs in skin immunity, the mobilization of LCs to regional lymph nodes as well as the recruitment of LC precursors from the circulation into the skin must be tightly regulated events. Although we are beginning to understand the mechanisms that regulate the migration of LCs from the epidermis to regional LNs during inflammatory

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“…< D'autres types de DC, dénommées DC dermiques ou interstitielles, moins bien caractéri-sées, sont présentes dans le tissu conjonctif (le derme cutané et la lamina propria muqueuse) [2]. Certaines de ces cellules sont phénotypique-ment et fonctionnellement similaires aux monocytes et pourraient constituer des précurseurs de CL [3]. La distribution des DC dans les tissus muqueux varie selon la nature de l'épithélium de revêtement et l'état inflammatoire du tissu.…”

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