Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation

Yasmin, Nighat; Bauer, Thomas; Modak, Madhura; Wagner, Karin; Schuster, Christopher; Köffel, René; Seyerl, Maria; Stöckl, Johannes; Elbe‐Bürger, Adelheid; Graf, Daniel; Strobl, Herbert

doi:10.1084/jem.20130275

Cited by 87 publications

(101 citation statements)

References 61 publications

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“…3B). These results confirmed that BMP-7 can readily replace TGF-b1 to induce langerin high LC-like cells as proposed by others (40). We additionally reported no additive or synergistic effect of those factors when put together on differentiating cells (Fig.…”

Section: Resultssupporting

confidence: 91%

“…In line with this, sparse studies reported basal GM-CSF synthesis in human and murine skin or colonic mucosa, most predominantly by KCs and fibroblasts (66)(67)(68). Interestingly, Yasmin et al (40) have clearly shown that BMP-7 precedes TGF-b1 during embryonic life, between 8-10 and 9-11 wk estimated gestational age, respectively (69). Both cytokines are still expressed in adult skin basally and suprabasally, respectively (40).…”

Section: Discussionmentioning

confidence: 93%

“…BMP-7 can replace TGF-b1 to induce langerin high MDLCs BMP-7 has been recently described as a key factor to differentiate LC-like cells from bone marrow precursors (40). We therefore wondered whether BMP-7 could act similarly to TGF-b1 on monocytes in association with GM-CSF.…”

Section: Resultsmentioning

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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Section: Resultssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 93%

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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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“…BMP7 signaling was reported to play a critical role in LC development (11). A recent study (13) (14) recently reported that Irf8 expression leads to an increase in Id2 transcript levels.…”

Section: Resultsmentioning

confidence: 99%

“…TGF-b promotes the development of DCs, and TGF-b-null mice have a defect in the development of epidermal Langerhans cells (LCs) (9,10). A recent study (11) identified another TGF-b superfamily ligand, BMP7, as an instructive factor for human epidermal LCs. TGF-b1 was reported to upregulate Irf8 during DC development (12).…”

mentioning

confidence: 99%

Cutting Edge: ACVRL1 Signaling Augments CD8α+ Dendritic Cell Development

Verma

Jaiswal

Chauhan

et al. 2016

The Journal of Immunology

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Dendritic cells (DCs) are a collection of different subtypes, each of which is characterized by specific surface markers, gene-expression patterns, and distinct functions. Members of the IFN regulatory factor family play critical roles in DC development and functions. Recently, Irf8 was shown to activate TGF-β signaling, which led to exacerbated neuroinflammation in the experimental autoimmune encephalomyelitis mouse model. We analyzed the effect of Irf8 on TGF-β/bone morphogenetic protein pathway–specific genes in DCs and identified Acvrl1, a type I TGF-β superfamily receptor, as a gene strongly induced by Irf8 expression. Among various DC subtypes, Acvrl1 is differentially expressed in CD8α+ DCs. ACVRL1 signaling augmented Irf8-directed classical CD8α+ DC development. Irf8 expression is essential for plasmacytoid DC and CD8α+ DC development, and this study demonstrates that ACVRL1 signaling plays a pivotal role whereby it suppresses plasmacytoid DC development while enhancing that of CD8α+ DCs, thus contributing to DC diversity development.

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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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Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation

Abstract: Bone morphogenetic protein 7 (BMP7) promotes the differentiation of Langerhans cells in the epidermis during prenatal development.

Cited by 87 publications

References 61 publications

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

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

Cutting Edge: ACVRL1 Signaling Augments CD8α+ Dendritic Cell Development

Origins and diversity of macrophages in health and disease

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