Two Distinct Types of Langerhans Cells Populate the Skin during Steady State and Inflammation

Seré, Kristin; Baek, Jea-Hyun; Ober‐Blöbaum, Julia L.; Müller‐Newen, Gerhard; Tacke, Frank; Yokota, Yoshifumi; Zenke, Martin; Hieronymus, Thomas

doi:10.1016/j.immuni.2012.07.019

Cited by 172 publications

(195 citation statements)

References 50 publications

(97 reference statements)

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“…Based on this knowledge, we reasoned that Ln + dDCs were important for activating CD8 + T cells following intradermal administration of plasmid DNA (23). Nevertheless, it is becoming increasingly clear that, under inflammatory conditions, LCs rapidly repopulate the skin (15,16), as was also observed in our experiments (Fig. 4C, 4D).…”

Section: Secondary Lcs Are Crucial For Optimal Cd8supporting

confidence: 74%

“…Under severe inflammatory conditions damaging the epidermis and eliminating large numbers of LCs, these cells can differentiate from bone marrow-derived precursors, either circulating or located in the epidermis (14)(15)(16). Repopulation of LCs can also occur from self-renewing epidermal precursors during moderate inflammation, similar to the situation in the steady-state (17,18).…”

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confidence: 97%

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Second-Generation Langerhans Cells Originating from Epidermal Precursors Are Essential for CD8+ T Cell Priming

Elnekave

Furmanov

Shaul

et al. 2014

The Journal of Immunology

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In vivo studies questioned the ability of Langerhans cells (LCs) to mediate CD8+ T cell priming. To address this issue, we used intradermal immunization with plasmid DNA, a system in which activation of CD8+ T cells depends on delayed kinetics of Ag presentation. We found that dendritic cells (DCs) located in the skin at the time of immunization have limited ability to activate CD8+ T cells. This activity was mediated by a second generation of DCs that differentiated in the skin several days after immunization, as well as by lymph node–resident DCs. Intriguingly, CD8+ T cell responses were not affected following treatment with clodronate liposomes, immunization of CCR2−/− mice, or local neutralization of CCL20. This suggests that local, rather than blood-derived, DC precursors mediate CD8+ T cell priming. Analysis of DC differentiation in the immunized skin revealed a gradual increase in the number of CD11c+ cells, which reached their maximum 2 wk after immunization. A similar differentiation kinetics was observed for LCs, with the majority of differentiating LCs proliferating in situ from epidermal precursors. By using B6/Langerin–diphtheria toxin receptor chimeric mice and LC ablation, we demonstrated that epidermal LCs were crucial for the elicitation of CD8+ T cell responses in vivo. Furthermore, LCs isolated from lymph nodes 2 wk after immunization contained the immunization plasmid and directly activated Ag-specific CD8+ T cells ex vivo. Thus, these results indicate that second-generation Ag-expressing LCs differentiating from epidermal precursors directly prime CD8+ T cells and are essential for optimal cellular immune responses following immunization with plasmid DNA.

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Section: Secondary Lcs Are Crucial For Optimal Cd8supporting

confidence: 74%

mentioning

confidence: 97%

Second-Generation Langerhans Cells Originating from Epidermal Precursors Are Essential for CD8+ T Cell Priming

Elnekave

Furmanov

Shaul

et al. 2014

The Journal of Immunology

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“…Under inflammatory stimuli, LCs become mature and leave their tissue to reach lymph nodes where they elicit specific T cell responses (3). In mice, it has been shown that inflamed tissues are rapidly replenished by a first wave of LCs developing from Gr-1 high monocytes and are characterized by a short half-life (8,9). In humans, it is not clear whether this occurs or not.…”

Section: Discussionmentioning

confidence: 99%

“…These precursors are endowed with local self-renewing properties allowing LC replenishment of peripheral tissues after inflammation resolution (7). However, under inflammation, Ly6C high monocytes were shown to give rise to short-term LCs in mice (8,9). These cells are then replaced by long-term LCs arising from the self-renewing precursors described above (9).…”

mentioning

confidence: 99%

“…However, under inflammation, Ly6C high monocytes were shown to give rise to short-term LCs in mice (8,9). These cells are then replaced by long-term LCs arising from the self-renewing precursors described above (9). In humans, convincing evidence that the LC network is reconstituted through proliferation of epithelium-residing precursors has come from stem cells (10,11) or solid organ transplantation (12,13).…”

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confidence: 99%

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Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

Picarda

Chéneau

Humbert

et al. 2016

The Journal of Immunology

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Langerhans cells (LCs) are epithelial APCs that sense danger signals and in turn trigger specific immune responses. In steady-state, they participate in the maintenance of peripheral tolerance to self-antigens whereas under inflammation LCs efficiently trigger immune responses in secondary lymphoid organs. It has been demonstrated in mice that LC-deprived epithelia are rapidly replenished by short half-life langerin-expressing monocyte-derived LCs (MDLCs). These surrogate LCs are thought to be progressively replaced by langerinhigh LCs arising from self-renewing epithelial precursors of hematopoietic origin. How LCs arise from blood monocytes is not fully understood. Hence, we sought to characterize key factors that induce differentiation of langerinhigh-expressing monocyte-derived Langerhans-like cells. We identified GM-CSF and TGF-β1 as key cytokines to generate langerinhigh-expressing cells but only in serum-free conditions. These cells were shown to express the LC-specific TROP-2 and Axl surface markers and contained Birbeck granules. Surprisingly, E-cadherin was not spontaneously expressed by these cells but required a direct contact with keratinocytes to be stably induced. MDLCs induced stronger allogeneic T cell proliferations but released low amounts of inflammatory cytokines upon TLR stimulation compared with donor-paired monocyte-derived dendritic cells. Immature langerinhigh MDLCs were responsive to MIP-3β/CCL20 and CTAC/CCL27 chemokine stimulations. Finally, we demonstrated that those cells behaved as bona fide LCs when inserted in a three-dimensional rebuilt epithelium by becoming activated upon TLR or UV light stimulations. Collectively, these results prompt us to propose these langerinhigh MDLCs as a relevant model to address LC biology–related questions.

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Origins and diversity of macrophages in health and disease

et al. 2020

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Macrophages are the first immune cells in the developing embryo and have a central role in organ development, homeostasis, immunity and repair. Over the last century, our understanding of these cells has evolved from being thought of as simple phagocytic cells to master regulators involved in governing a myriad of cellular processes. A better appreciation of macrophage biology has been matched with a clearer understanding of their diverse origins and the flexibility of their metabolic and transcriptional machinery. The understanding of the classical mononuclear phagocyte system in its original form has now been expanded to include the embryonic origin of tissue‐resident macrophages. A better knowledge of the intrinsic similarities and differences between macrophages of embryonic or monocyte origin has highlighted the importance of ontogeny in macrophage dysfunction in disease. In this review, we provide an update on origin and classification of tissue macrophages, the mechanisms of macrophage specialisation and their role in health and disease. The importance of the macrophage niche in providing trophic factors and a specialised environment for macrophage differentiation and specialisation is also discussed.

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Two Distinct Types of Langerhans Cells Populate the Skin during Steady State and Inflammation

Cited by 172 publications

References 50 publications

Second-Generation Langerhans Cells Originating from Epidermal Precursors Are Essential for CD8+ T Cell Priming

Second-Generation Langerhans Cells Originating from Epidermal Precursors Are Essential for CD8+ T Cell Priming

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

Origins and diversity of macrophages in health and disease

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