Skin-resident immune cells actively coordinate their distribution with epidermal cells during homeostasis

Park, Sangbum; Matte-Martone, Catherine; Gonzalez, David G.; Lathrop, Elizabeth; May, Dennis; Pineda, Cristiana M.; Moore, Jessica L.; Boucher, Jonathan; Marsh, Edward; Schmitter-Sánchez, Axel; Cockburn, Katie; Маркова, О. В.; Bellaı̈che, Yohanns; Greco, Valentina

doi:10.1038/s41556-021-00670-5

Cited by 40 publications

(38 citation statements)

References 72 publications

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“…Our data derived from the Lrig1 -KO model, characterized by progressive scale fusion, point to remarkably stable LC densities during interscale shrinkage and hence adaptation of the LC network to changes in scale:interscale IFE ratios. Though not directly comparable, this partly resembles the recently reported modulation of LC numbers upon alterations of KC densities in adult, non-patterned orthokeratotic ear epidermis (Park et al, 2021). These combined findings illustrate previously unrecognized dynamics of resident immune cells and their ability to adapt to changes in tissue epithelia.…”

Section: Discussionsupporting

confidence: 86%

“…The interfollicular epidermis (IFE) of murine ear and back-skin harbours evenly distributed immune cells (Bergstresser et al, 1980) and is largely devoid of MCs, which mostly reside in the dermis (Hirobe, 1984; Kunisada et al, 2000). In adult ear epidermis, LCs and DETCs actively maintain a non-random distribution that depends on KC density and engages LC- expressed Rac1 (Park et al, 2021), yet the molecular mechanisms how KCs control resident immune cells remain open. Tail skin instead exhibits two distinct epidermal compartments: ‘Scale’ IFE forms a spherical epidermal patch just above hair-follicle triplets and undergoes parakeratotic differentiation, characterized by lack of a granular layer and nucleated cornified layer KCs.…”

Section: Introductionmentioning

confidence: 99%

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Lrig1 and Wnt dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis

Baess

Graband

Seré

et al. 2021

Preprint

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The barrier-forming, self-renewing mammalian epidermis comprises keratinocytes, pigment-producing melanocytes, and resident immune cells as first-line host defense. In murine tail skin, interfollicular epidermis patterns into pigmented ′scale′ and non-pigmented ′interscale′ epidermis. Why and how mature melanocytes confine to scale epidermis is unresolved. Here, we delineate a cellular hierarchy among epidermal cell types that determines skin patterning. Already during postnatal development, melanocytes co-segregate with newly forming scale compartments. Intriguingly, this process coincides with partitioning of both Langerhans cells and dendritic epidermal T-cells to interscale epidermis, suggesting functional segregation of pigmentation and immune surveillance. Analysis of non-pigmented mice and of mice lacking melanocytes or resident immune cells revealed that immunocyte patterning is melanocyte- and melanin-independent, and, vice versa, immune cells do not control melanocyte localization. Instead, genetically enforced progressive scale fusion upon Lrig1 deletion showed that melanocytes and immune cells dynamically follow epithelial scale:interscale patterns. Importantly, disrupting Wnt-Lef1 function in keratinocytes caused melanocyte mislocalization to interscale epidermis, implicating canonical Wnt signaling in organizing the pigmentation pattern. Together, this work uncovered cellular and molecular principles underlying the compartmentalization of tissue functions in skin.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Lrig1 and Wnt dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis

Baess

Graband

Seré

et al. 2021

Preprint

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“…These cells balance self-renewal and differentiation behaviors to maintain homeostasis over the lifetime of the animal. Recent work has provided evidence of local coordination of these behaviors, where cell fates are influenced by their direct neighbors [8], but also of large-scale organization, where dynamic behaviours of diverse cell types are coordinated [15,16]. In this highly regenerative tissue, communication between stem cells is necessary to carry out this coordination at different scales.…”

Section: Introductionmentioning

confidence: 99%

G2 stem cells orchestrate time-directed, long-range coordination of calcium signaling during skin epidermal regeneration

Moore

Gao

Matte-Martone

et al. 2021

Preprint

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Regenerative processes in the mammalian skin require coordinated cell-cell communication. Ca2+ signaling can coordinate tissue-level responses in developing and wounded epithelia in tissue explants and invertebrates. However, its role in the homeostatic, regenerative basal layer of the skin epithelium is unknown due to significant challenges in studying signaling dynamics in a spatially complex tissue context in live mice. Here we combine in vivo imaging of dynamic Ca2+ signaling at the single cell level across thousands of cells with a novel computational approach, Geometric Scattering Trajectory Homology (GSTH). GSTH models Ca2+ as signals over a cell adjacency graph and uses a multi-level wavelet-like transform (called a scattering transform) to extract signaling patterns from our high dimensional in vivo datasets. We discover local Ca2+ signaling patterns are orchestrated so that signals flow in a coordinated and directed manner across the tissue, distinct from topographically uncoordinated Ca2+ signaling in excitatory tissues. Directed Ca2+ signaling is regulated by the major gap junction protein in the epidermal stem cell layer, Connexin 43 (Cx43). Cx43 gap junctions are dissociated as cells progress through the cell cycle out of G1 and play an essential role in the progression of stem cells from G2 towards mitosis. Finally, G2 cells display related signaling patterns and are essential for tissue-level signaling coordination. Together, our results provide insight into how such a ubiquitous signaling pathway regulates highly specific behaviors and outcomes at a tissue-wide level to maintain proper homeostasis.

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“…The skin is composed of stratified epithelium with a dry surface, whereas the intestine is a simple squamous epithelium and has many nutrients on the surface which favors the microbiome ( Grice and Segre, 2011 ; Byrd et al, 2018 ; Fan and Pedersen, 2021 ). Recently, it has been shown that LCs and DETCs actively maintain their regular distribution during homeostasis ( Park et al, 2021 ). Remarkably, these immune cells recover regular distribution within a few days after local perturbation with laser ablation and after global depletion with diphtheria toxin-induced cell death.…”

Section: Introductionmentioning

confidence: 99%

“…It is revealed that dendritic interaction is important for maintaining a regular distribution, but the underlying mechanisms remain unclear. Interestingly, depletions of one immune population do not impact the other’s patterning ( Park et al, 2021 ). These data suggest that although LCs and DETCs have a similar tiling pattern, these cells maintain the pattern independently through different mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Building vs. Rebuilding Epidermis: Comparison Embryonic Development and Adult Wound Repair

Park

2022

Front. Cell Dev. Biol.

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Wound repair is essential to restore tissue function through the rebuilding of pre-existing structures. The repair process involves the re-formation of tissue, which was originally generated by embryonic development, with as similar a structure as possible. Therefore, these two processes share many similarities in terms of creating tissue architecture. However, fundamental differences still exist, such as differences in the cellular components, the status of neighboring tissues, and the surrounding environment. Recent advances in single-cell transcriptomics, in vivo lineage tracing, and intravital imaging revealed subpopulations, long-term cell fates, and dynamic cellular behaviors in live animals that were not detectable previously. This review highlights similarities and differences between adult wound repair and embryonic tissue development with a particular emphasis on the epidermis of the skin.

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Skin-resident immune cells actively coordinate their distribution with epidermal cells during homeostasis

Abstract: Reprints and permissions information is available at www.nature.com/reprints.

Cited by 40 publications

References 72 publications

Lrig1 and Wnt dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis

Lrig1 and Wnt dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis

G2 stem cells orchestrate time-directed, long-range coordination of calcium signaling during skin epidermal regeneration

Building vs. Rebuilding Epidermis: Comparison Embryonic Development and Adult Wound Repair

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