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Immunosuppressive Properties of Epidermal Keratinocytes Differ According to Their Immaturity Status.

ABSTRACT: Preservation of a functional keratinocyte stem cell pool is essential to ensure the long-term maintenance of epidermis integrity, through continuous physiological renewal and regeneration in case of injury. Protecting stem cells from inflammation and immune reactions is thus a critical issue that needs to be explored. Here, we show that the immature CD49f^high precursor cell fraction from interfollicular epidermis keratinocytes, comprising stem cells and progenitors, is able to inhibit CD4 ⁺ T-cell proliferation. Of note, both the stem cell-enriched CD49f^high/EGFR^low subpopulation and the less immature CD49f^high/EGFR^high progenitors ensure this effect. Moreover, we show that HLA-G and PD-L1 immune checkpoints are overexpressed in CD49f^high precursors, as compared to CD49f^low differentiated keratinocytes. This potency may limit immune reactions against immature precursors including stem cells, and protect them from exacerbated inflammation. Further exploring this correlation between immuno-modulation and immaturity may open perspectives in allogenic cell therapies.

SUBMITTER: Mestrallet G

PROVIDER: S-EPMC8878806 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Immunosuppressive Properties of Epidermal Keratinocytes Differ According to Their Immaturity Status.

Mestrallet Guillaume G Carosella Edgardo D ED Martin Michele T MT Rouas-Freiss Nathalie N Fortunel Nicolas O NO LeMaoult Joel J

Frontiers in immunology 20220211

Preservation of a functional keratinocyte stem cell pool is essential to ensure the long-term maintenance of epidermis integrity, through continuous physiological renewal and regeneration in case of injury. Protecting stem cells from inflammation and immune reactions is thus a critical issue that needs to be explored. Here, we show that the immature CD49f<sup>high</sup> precursor cell fraction from interfollicular epidermis keratinocytes, comprising stem cells and progenitors, is able to inhibit ...[more]

PMID: 35222373

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Project description:BackgroundNon-communicable diseases (NCDs) are increased amongst people living with HIV (PLWH) and are driven by persistent immune activation. The role of socioeconomic status (SES) in immune activation amongst PLWH is unknown, especially in low-income sub-Saharan Africa (SSA), where such impacts may be particularly severe.MethodsWe recruited Malawian adults with CD4<100 cells/ul two weeks after starting ART in the REALITY trial (NCT01825031), as well as volunteers without HIV infection. Clinical assessment, socioeconomic evaluation, blood draw for immune activation markers and carotid femoral pulse wave velocity (cfPWV) were carried out at 2- and 42-weeks post-ART initiation. Socioeconomic risk factors for immune activation and arterial stiffness were assessed using linear regression models.ResultsOf 279 PLWH, the median (IQR) age was 36 (31-43) years and 122 (44%) were female. Activated CD8 T-cells increased from 70% amongst those with no education to 88% amongst those with a tertiary education (p = 0.002); and from 71% amongst those earning less than 10 USD/month to 87% amongst those earning between 100-150 USD/month (p = 0.0001). Arterial stiffness was also associated with higher SES (car ownership p = 0.003, television ownership p = 0.012 and electricity access p = 0.029). Conversely, intermediate monocytes were higher amongst those with no education compared to a tertiary education (12.6% versus 7.3%; p = 0.01) and trended towards being higher amongst those earning less than 10 USD/month compared to 100-150 USD/month (10.5% versus 8.0%; p = 0.08). Water kiosk use showed a protective association against T cell activation (p = 0.007), as well as endothelial damage (MIP1β, sICAM1 and sVCAM1 p = 0.047, 0.026 and 0.031 respectively).ConclusionsSocioeconomic risk factors for persistent inflammation amongst PLWH in SSA differ depending on the type of inflammatory pathway. Understanding these pathways and their socioeconomic drivers will help identify those at risk and target interventions for NCDs. Future studies assessing drivers of inflammation in HIV should include an SES assessment.

Project description:We hypothesized that treatment of the injured skin with occlusion limits TEWL and results in a phenotype of epithelial response that more closely resembles mucosa. Here we addressed whether different hydration conditions change gene expression patterns in epidermis using microarray study in rabbit partial-thickness incisional wound. Microarray on epidermis showed that global expression patterns of the genes in full occluded vs. non-occluded wounds are distinct. Many genes - including IL-1M-NM-2, IL-8, TNF-M-NM-1, and COX-2-upregulated in skin environment were also upregulated in non-occluded wounds. Simulating increased TEWL showed increased expression of proinflammatory genes in human ex vivo skin culture (HESC) and stratified keratinocytes. Microarray on epidermis showed that global expression patterns of the genes in full occluded vs. non-occluded wounds are distinct. Female New Zealand White rabbits (3-4 kg) were purchased from Covance (Princeton, NJ) and were acclimated for a minimum of 7 days prior to experiments. Ketamine (45 mg/kg) and xylazine (7 mg/kg) were injected intramuscularly as primary anesthesia method prior to the procedure. The procedure was performed while the animal was in full anesthesia with the vital sign checking every 15 min including heart beat, breath frequency, and body temperature. Buprenex (0.05 mg/kg) was applied by intradermal injection prior to the surgery and continued every 6-12 hours for 24 hours after surgery. The animals were all monitored closely for signs of discomfort post surgeries. Tissue harvests were performed following euthanasia. The superficial incisional grids on rabbit ear were created by using a double blade scalpel with 1 mm space between the two blades. A single layer of Tegaderm was used to cover the wounding areas on both right and left ears until the wounding areas were fully re-epithelialized (two days post wounding, POE0). Thereafter, the Tegaderm on right ear was completely removed (NOW) while four more layers of Tegaderms were applied on left ear wounds (FOW). Rabbit ear samples were harvested at POE0, POE3 and POE5.

Dataset Information

Immunosuppressive Properties of Epidermal Keratinocytes Differ According to Their Immaturity Status.

Publications

Immunosuppressive Properties of Epidermal Keratinocytes Differ According to Their Immaturity Status.

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