Loss of T cell tolerance in the skin following immunopathology is linked to failed restoration of the dermal niche by recruited macrophages

West, Heather C.; Davies, James; Henderson, Stephen; Adegun, Oluyori Kutulola; Ward, Sophie; Ferrer, Ivana R.; Tye, Chanidapa Adele; Vallejo, Andrés F.; Jardine, Laura; Collin, Matthew; Polak, Marta E.; Bennett, Clare

doi:10.1016/j.celrep.2022.110819

Cited by 3 publications

(8 citation statements)

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“…But, LCs express high levels of CD24 and Zbtb46, considered markers of conventional DCs (Wu et al ., 2016), moreover activation and migration initiates the expression of convergent transcriptional program shared with DC populations leaving the skin (Clayton et al ., 2017; Polak and Singh, 2021; Reynolds et al ., 2021). Migrating LCs upregulate an IRF4-dependent gene program which is also evident in moDC (Sirvent et al ., 2020; Davies et al ., 2022). We believe our data begin to reconcile this dichotomy.…”

Section: Discussionmentioning

confidence: 99%

“…Tissue processing. Murine skin: Epidermal single cell suspensions were generated as described (Ferrer et al, 2019;West et al, 2022). Dorsal and ventral sides of the ear pinna were split using forceps.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, Zeb2 was highly negatively correlated with expression of the LC-defining transcription factors Id2 and the aryl hydrocarbon receptor (Ahr) that are also upregulated by eLCs in utero (Mass et al 2016) (Figures 4 A-C). Mirroring DCs that migrate out of the skin, migratory mLCs were defined by upregulation of Irf4, Rel and Nr4a3 (Figure S4A) (Baratin et al 2015;Sirvent et al, 2020;Reynolds et al 2021;Davies et al, 2022).…”

Section: Monocyte Ontogeny Determines Mlc Repopulationmentioning

confidence: 99%

“…Epidermal monocytes also down- 4 A-C). Mirroring DCs that migrate out of the skin, migratory mLCs were defined by upregulation of Irf4, Rel and Nr4a3 (Figure S4A) (Baratin et al 2015;Sirvent et al, 2020;Reynolds et al 2021;Davies et al, 2022).…”

Section: Metabolic Adaptation Of Resident Mlc But Not Mrc1mentioning

confidence: 99%

“…Expression of Zeb2 was mutually exclusive to Epcam-expressing cells (Figures 4B, C), suggesting that, unlike other resident 4 A-C). Mirroring DCs that migrate out of the skin, migratory mLCs were defined by upregulation of Irf4, Rel and Nr4a3 (Figure S4A) (Baratin et al 2015;Sirvent et al, 2020;Reynolds et al 2021;Davies et al, 2022).…”

Section: )mentioning

confidence: 99%

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Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Appios,

Davies,

Sirvent

et al. 2023

Preprint

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Langerhans cells (LCs) are a unique population of phagocytes programmed within embryonic skin to maintain tissue and immunological homeostasis at the epidermal barrier site. Unique amongst tissue-resident macrophages, LCs play roles in skin innervation and repair, while also functioning as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DC). We currently lack insight into the molecular pathways that determine this dichotomy, when they are established, and whether precursors recruited to the adult skin niche access the same instructive signals laid downin utero. Tracking differentiation of monocyte-derived (m)LCs after destruction of embryo-derived cells in murine adult skin, we reveal intrinsic intra-epidermal heterogeneity and selection of MDP-monocytes to by-pass gene programs specifying a macrophage fate. Within the adult skin, we demonstrate that the hair follicle niche provides Notch signals that determine commitment to become resident mLCs. Using a unique human LC dataset, we show that embryo-derived (e)LCs in newborn human skin retain transcriptional evidence of their macrophage origin, but this is superseded by distinct DC-like immune modules after expansion of the eLC network. Thus, convergent differentiation of monocytes within adult skin replicates conditioning of eLC to-wards more immunogenic DC-like cells within post-natal skin.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Monocyte Ontogeny Determines Mlc Repopulationmentioning

confidence: 99%

Section: Metabolic Adaptation Of Resident Mlc But Not Mrc1mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

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Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Appios,

Davies,

Sirvent

et al. 2023

Preprint

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Metabolic adaption of mucosal macrophages: Is metabolism a driver of persistence across tissues?

Bennett

Perona-Wright

2023

Mucosal Immunology

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Complex interactions of cellular players in chronic Graft-versus-Host Disease

et al. 2023

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Chronic Graft-versus-Host Disease is a life-threatening inflammatory condition that affects many patients after allogeneic hematopoietic stem cell transplantation. Although we have made substantial progress in understanding disease pathogenesis and the role of specific immune cell subsets, treatment options are still limited. To date, we lack a global understanding of the interplay between the different cellular players involved, in the affected tissues and at different stages of disease development and progression. In this review we summarize our current knowledge on pathogenic and protective mechanisms elicited by the major involved immune subsets, being T cells, B cells, NK cells and antigen presenting cells, as well as the microbiome, with a special focus on intercellular communication of these cell types via extracellular vesicles as up-and-coming fields in chronic Graft-versus-Host Disease research. Lastly, we discuss the importance of understanding systemic and local aberrant cell communication during disease for defining better biomarkers and therapeutic targets, eventually enabling the design of personalized treatment schemes.

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Loss of T cell tolerance in the skin following immunopathology is linked to failed restoration of the dermal niche by recruited macrophages

Cited by 3 publications

References 69 publications

Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Metabolic adaption of mucosal macrophages: Is metabolism a driver of persistence across tissues?

Complex interactions of cellular players in chronic Graft-versus-Host Disease

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