Development of Blood and Lymphatic Endothelial Cells in Embryonic and Fetal Human Skin

Schuster, Christopher; Mildner, Michael; Botta, Albert; Nemec, Lucas; Rogojanu, Radu; Beer, Lucian; Fiala, Christian; Eppel, Wolfgang; Bauer, Wolfgang; Petzelbauer, Peter; Elbe‐Bürger, Adelheid

doi:10.1016/j.ajpath.2015.05.006

Cited by 10 publications

(8 citation statements)

References 52 publications

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“…Our data are consistent with reports of the Schuster‐ and Elbe‐Bürger group that show low numbers of macrophages, dendritic cells, and Langerhans cells in human fetal skin . In accordance with the data of Coolen et al and Schuster et al, no significant differences in the vascular network were observed either between fetal and adult skin. Furthermore, staining with early lineage marker CD45 showed significantly lower levels of CD45 + ‐cells in fetal skin compared to adult skin while fetal lymph nodes at this gestational age contained sufficient levels of CD45 + ‐cells comparable to adult lymph nodes.…”

Section: Discussionsupporting

confidence: 94%

Healthy human second‐trimester fetal skin is deficient in leukocytes and associated homing chemokines

Walraven

Talhout

Beelen

et al. 2016

Wound Repair Regeneration

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The lack of immune cells in mid-gestational fetal skin is often mentioned as a key factor underlying scarless healing. However, the scarless healing ability is conserved until long after the immune system in the fetus is fully developed. Therefore, we studied human second-trimester fetal skin and compared the numbers of immune cells and chemokine levels from fetal skin with adult skin. By using immunohistochemistry, we show that healthy fetal skin contains significant lower numbers of CD68(+) -macrophages, Tryptase(+) -mast cells, Langerin(+) -Langerhans cells, CD1a(+) -dendritic cells, and CD3(+) -T cells compared to adult skin. Staining with an early lineage leukocyte marker, i.e., CD45, verified that the number of CD45(+) -immune cells was indeed significantly lower in fetal skin but that sufficient numbers of immune cells were present in the fetal lymph node. No differences in the vascular network were observed between fetal and adult skin. Moreover, significant lower levels of lymphocyte chemokines CCL17, CCL21, and CCL27 were observed in fetal skin. However, levels of inflammatory interleukins such as IL-6, IL-8, and IL-10 were undetectable and levels of CCL2 were similar in healthy fetal and adult skin. In conclusion, this study shows that second-trimester fetal skin contains low levels of immune cells and leukocyte chemokines compared to adult skin. This immune cell deficiency includes CD45(+) leukocytes, despite the abundant presence of these cells in the lymph node. The immune deficiency in healthy second-trimester fetal skin may result in reduced inflammation during wound healing, and could underlie the scarless healing capacities of the fetal skin.

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Section: Discussionsupporting

confidence: 94%

Healthy human second‐trimester fetal skin is deficient in leukocytes and associated homing chemokines

Walraven

Talhout

Beelen

et al. 2016

Wound Repair Regeneration

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“…Both LE and VE are present in 7 PCW fetal skin, earlier than previous studies using 8-10 PCW skin (26). Fetal lymphatic endothelial cells have lower expression of LYVE1, PDPN and CCL21 suggesting that they are functionally immature (Fig.…”

Section: Specialized Vascular Endothelium Mediates Leukocyte Traffickingmentioning

confidence: 54%

Poised cell circuits in human skin are activated in disease

Reynolds

Végh

Fletcher

et al. 2020

Preprint

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The human skin confers biophysical and immunological protection through a complex cellular network that is established early in development. We profiled ~500,000 single cells using RNA-sequencing from healthy adult and developing skin, and skin from patients with atopic dermatitis and psoriasis. Our findings reveal a predominance of innate lymphoid cells and macrophages in developing skin in contrast to T cells and migratory dendritic cells in adult skin. We demonstrate dual keratinocyte differentiation trajectories and activated cellular circuits comprising vascular endothelial cells mediating immune cell trafficking, disease specific clonally expanded IL13/IL22 and IL17A/F-expressing lymphocytes, epidermal IL23-expressing dendritic cells and inflammatory keratinocytes in disease. Our findings provide key insights into the dynamic cellular landscape of human skin in health and disease.

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“…In summary, our data suggest that fetal skin and gut DC have the capacity to migrate through lymphatics and to lymph nodes from 16wk EGA, where they may interact with fetal T cells that are present in lymphoid organs from 10wk EGA16. The reason for the initiation of DC migration to the lymph nodes around 16wk EGA remains unclear: while the human lymphatic system is structurally complete by 8wk EGA, it may remain functionally immature for some time thereafter17.…”

mentioning

confidence: 83%

Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2

McGovern

Shin

Low

et al. 2017

Nature

Self Cite

217

202

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During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.

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Development of Blood and Lymphatic Endothelial Cells in Embryonic and Fetal Human Skin

Cited by 10 publications

References 52 publications

Healthy human second‐trimester fetal skin is deficient in leukocytes and associated homing chemokines

Healthy human second‐trimester fetal skin is deficient in leukocytes and associated homing chemokines

Poised cell circuits in human skin are activated in disease

Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2

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