Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion

Science ◽  
2021 ◽  
Vol 373 (6554) ◽  
pp. eabd2893
Author(s):  
Ruth Choa ◽  
Junichiro Tohyama ◽  
Shogo Wada ◽  
Hu Meng ◽  
Jian Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Steady State ◽  
Immune System ◽  
Skin Barrier ◽  
Thymic Stromal Lymphopoietin ◽  
Skin Barrier Function ◽  
Peptide Expression ◽  
Antimicrobial Peptide Expression ◽  
Sebum Secretion

Emerging studies indicate that the immune system can regulate systemic metabolism. Here, we show that thymic stromal lymphopoietin (TSLP) stimulates T cells to induce selective white adipose loss, which protects against obesity, improves glucose metabolism, and mitigates nonalcoholic steatohepatitis. Unexpectedly, adipose loss was not caused by alterations in food intake, absorption, or energy expenditure. Rather, it was induced by the excessive loss of lipids through the skin as sebum. TSLP and T cells regulated sebum release and sebum-associated antimicrobial peptide expression in the steady state. In human skin, TSLP expression correlated directly with sebum-associated gene expression. Thus, we establish a paradigm in which adipose loss can be achieved by means of sebum hypersecretion and uncover a role for adaptive immunity in skin barrier function through sebum secretion.

scholarly journals Assessment of Human Skin Gene Expression by Different Blends of Plant Extracts with Implications to Periorbital Skin Aging

2018 ◽  
Vol 19 (11) ◽  
pp. 3349 ◽  
Author(s):  
Jin Namkoong ◽  
Dale Kern ◽  
Helen Knaggs
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Human Skin ◽  
Barrier Function ◽  
Skin Barrier ◽  
Skin Aging ◽  
Skin Barrier Function ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
And Oxidative Stress

Since the skin is the major protective barrier of the body, it is affected by intrinsic and extrinsic factors. Environmental influences such as ultraviolet (UV) irradiation, pollution or dry/cold air are involved in the generation of radical oxygen species (ROS) and impact skin aging and dermal health. Assessment of human skin gene expression and other biomarkers including epigenetic factors are used to evaluate the biological/molecular activities of key compounds in cosmetic formulas. The objective of this study was to quantify human gene expression when epidermal full-thickness skin equivalents were exposed to: (a) a mixture of betaine, pentylene glycol, Saccharomyces cerevisiae and Rhodiola rosea root extract (BlendE) for antioxidant, skin barrier function and oxidative stress (with hydrogen peroxide challenge); and (b) a mixture of Narcissus tazetta bulb extract and Schisandra chinensis fruit extract (BlendIP) for various biomarkers and microRNA analysis. For BlendE, several antioxidants, protective oxidative stress biomarkers and many skin barrier function parameters were significantly increased. When BlendE was evaluated, the negative impact of the hydrogen peroxide was significantly reduced for the matrix metalloproteinases (MMP 3 and MMP 12), the skin aging and oxidative stress biomarkers, namely FBN2, ANXA1 and HGF. When BlendIP was tested for cell proliferation and dermal structural components to enhance the integrity of the skin around the eyes: 8 growth factors, 7 signaling, 7 structural/barrier function and 7 oxidative stress biomarkers were significantly increased. Finally, when BlendIP was tested via real-time RT-PCR for microRNA expression: miR-146a, miR-22, miR155, miR16 and miR21 were all significantly increased over control levels. Therefore, human skin gene expression studies are important tools to assess active ingredient compounds such as plant extract blends to advance dermal hypotheses toward validating cosmetic formulations with botanical molecules.

Immune modulation property of Lactobacillus paracasei NCC2461 (ST11) strain and impact on skin defences

2014 ◽  
Vol 5 (2) ◽  
pp. 129-136 ◽  
Author(s):  
J. Benyacoub ◽  
N. Bosco ◽  
C. Blanchard ◽  
A. Demont ◽  
D. Philippe ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Modulation ◽  
Inflammatory Diseases ◽  
Skin Barrier ◽  
Probiotic Strain ◽  
Skin Barrier Function ◽  
Immune Functions ◽  
Skin Immune System ◽  
Skin Physiology ◽  
Immune Dysfunctions

The gut intestinal tract harbours a complex microbiota. Disturbances in the microbiota composition have been associated with several immune dysfunctions such as inflammatory diseases. Specific strains of probiotics have shown to beneficially influence the composition and/or metabolic activity of the endogenous microbiota. Taking advantage of the plasticity of the immune system, the probiotic strain NCC2461 (i.e. ST11 or CNCM I-2116) supports and/or restores homeostasis in reaction to different physiopathological conditions. The potential of NCC2461 to modulate both mucosal and systemic immune functions led us to test its impact on skin physiology. Even though clear mechanisms explaining gut-skin interaction are still lacking, a set of experimental and clinical data reviewed herein have shown that NCC2461 exerts its effects beyond the gut and confers benefits at the skin level. It contributes to the reinforcement of skin barrier function, decreases skin sensitivity and modulates the skin immune system leading to the preservation of skin homeostasis.

Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms

1988 ◽  
Vol 8 (9) ◽  
pp. 3820-3826
Author(s):  
T Lindsten ◽  
C H June ◽  
C B Thompson ◽  
J M Leiden
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Steady State ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Transcription Elongation ◽  
Fold Increase ◽  
Mrna Levels ◽  
Myristate Acetate

The 4F2 molecule belongs to the set of cell surface antigens which is induced following lectin- or antigen-mediated T-cell activation. The increase in 4F2 cell surface expression following lectin-mediated stimulation has been shown to be accompanied by a parallel increase in the steady-state levels of 4F2 heavy-chain (4F2HC) mRNA. The studies described in this report were designed to further elucidate the molecular mechanisms responsible for induction of 4F2HC gene expression following activation of normal resting human peripheral blood T cells. The low levels of mature 4F2HC mRNA in resting T cells were shown to be the result of a block to transcription elongation within the exon 1-intron 1 region of the 4F2HC gene rather than promoter inactivity. Phorbol myristate acetate stimulation of resting T cells resulted in a 20-fold increase in steady-state 4F2HC mRNA levels which was mediated by removal of this block to transcription elongation. The phorbol myristate acetate-induced increase in 4F2HC gene expression is distinct from previously described AP-1-mediated, phorbol ester-induced gene expression in that it requires new protein synthesis. Treatment of resting T cells with ionomycin plus PMA resulted in a 60-fold increase in 4F2HC mRNA levels. This induction was mediated by both an increase in promoter utilization and removal of the block to transcription elongation. Finally, by increasing the half-life of 4F2HC mRNA, cycloheximide treatment of resting T cells induced an approximately five fold increase in the levels of 4F2HC gene expression, although the physiologic significance of this mechanism remains unclear. These results demonstrate that the level of 4F2HC gene expression in normal peripheral blood T cells can be regulated by at least three distinct molecular pathways: (i) changes in promoter utilization, (ii) modulation of a block to transcription elongation, and (iii) alteration in mRNA stability.

scholarly journals Skin Barrier Dysfunction and Low Antimicrobial Peptide Expression in Cutaneous T-cell Lymphoma

2014 ◽  
Vol 20 (16) ◽  
pp. 4339-4348 ◽  
Author(s):  
Hiraku Suga ◽  
Makoto Sugaya ◽  
Tomomitsu Miyagaki ◽  
Hanako Ohmatsu ◽  
Makiko Kawaguchi ◽  
...  
Keyword(s):  
T Cell ◽  
Antimicrobial Peptide ◽  
Cell Lymphoma ◽  
Skin Barrier ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Barrier Dysfunction ◽  
Peptide Expression ◽  
Antimicrobial Peptide Expression

scholarly journals Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms.

1988 ◽  
Vol 8 (9) ◽  
pp. 3820-3826 ◽  
Author(s):  
T Lindsten ◽  
C H June ◽  
C B Thompson ◽  
J M Leiden
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Steady State ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Transcription Elongation ◽  
Fold Increase ◽  
Mrna Levels ◽  
Myristate Acetate

The 4F2 molecule belongs to the set of cell surface antigens which is induced following lectin- or antigen-mediated T-cell activation. The increase in 4F2 cell surface expression following lectin-mediated stimulation has been shown to be accompanied by a parallel increase in the steady-state levels of 4F2 heavy-chain (4F2HC) mRNA. The studies described in this report were designed to further elucidate the molecular mechanisms responsible for induction of 4F2HC gene expression following activation of normal resting human peripheral blood T cells. The low levels of mature 4F2HC mRNA in resting T cells were shown to be the result of a block to transcription elongation within the exon 1-intron 1 region of the 4F2HC gene rather than promoter inactivity. Phorbol myristate acetate stimulation of resting T cells resulted in a 20-fold increase in steady-state 4F2HC mRNA levels which was mediated by removal of this block to transcription elongation. The phorbol myristate acetate-induced increase in 4F2HC gene expression is distinct from previously described AP-1-mediated, phorbol ester-induced gene expression in that it requires new protein synthesis. Treatment of resting T cells with ionomycin plus PMA resulted in a 60-fold increase in 4F2HC mRNA levels. This induction was mediated by both an increase in promoter utilization and removal of the block to transcription elongation. Finally, by increasing the half-life of 4F2HC mRNA, cycloheximide treatment of resting T cells induced an approximately five fold increase in the levels of 4F2HC gene expression, although the physiologic significance of this mechanism remains unclear. These results demonstrate that the level of 4F2HC gene expression in normal peripheral blood T cells can be regulated by at least three distinct molecular pathways: (i) changes in promoter utilization, (ii) modulation of a block to transcription elongation, and (iii) alteration in mRNA stability.

scholarly journals Cyclic mechanical stretch down-regulates cathelicidin antimicrobial peptide expression and activates a pro-inflammatory response in human bronchial epithelial cells

PeerJ ◽  
2015 ◽  
Vol 3 ◽  
pp. e1483 ◽  
Author(s):  
Harpa Karadottir ◽  
Nikhil Nitin Kulkarni ◽  
Thorarinn Gudjonsson ◽  
Sigurbergur Karason ◽  
Gudmundur Hrafn Gudmundsson
Keyword(s):  
Gene Expression ◽  
Inflammatory Response ◽  
Antimicrobial Peptide ◽  
Mrna Expression ◽  
Inflammatory Responses ◽  
Cyclic Stretch ◽  
Down Regulation ◽  
Bronchial Epithelial ◽  
Peptide Expression ◽  
Antimicrobial Peptide Expression

Mechanical ventilation (MV) of patients can cause damage to bronchoalveolar epithelium, leading to a sterile inflammatory response, infection and in severe cases sepsis. Limited knowledge is available on the effects of MV on the innate immune defense system in the human lung. In this study, we demonstrate that cyclic stretch of the human bronchial epithelial cell lines VA10 and BCi NS 1.1 leads to down-regulation of cathelicidin antimicrobial peptide (CAMP) gene expression. We show that treatment of VA10 cells with vitamin D3 and/or 4-phenyl butyric acid counteracted cyclic stretch mediated down-regulation ofCAMPmRNA and protein expression (LL-37). Further, we observed an increase in pro-inflammatory responses in the VA10 cell line subjected to cyclic stretch. The mRNA expression of the genes encoding pro-inflammatory cytokines IL-8 and IL-1βwas increased after cyclic stretching, where as a decrease in gene expression of chemokines IP-10 and RANTES was observed. Cyclic stretch enhanced oxidative stress in the VA10 cells. The mRNA expression of toll-like receptor (TLR)3,TLR5andTLR8was reduced, while the gene expression ofTLR2was increased in VA10 cells after cyclic stretch. In conclusion, ourin vitroresults indicate that cyclic stretch may differentially modulate innate immunity by down-regulation of antimicrobial peptide expression and increase in pro-inflammatory responses.

scholarly journals Early Antiretroviral Therapy for Simian Immunodeficiency Virus Infection Leads to Mucosal CD4+ T-Cell Restoration and Enhanced Gene Expression Regulating Mucosal Repair and Regeneration

2005 ◽  
Vol 79 (5) ◽  
pp. 2709-2719 ◽  
Author(s):  
Michael D. George ◽  
Elizabeth Reay ◽  
Sumathi Sankaran ◽  
Satya Dandekar
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Simian Immunodeficiency Virus ◽  
Hiv Infections ◽  
Mucosal Immune System ◽  
T Cell Subsets ◽  
Immunodeficiency Virus

ABSTRACT Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections lead to rapid depletion of CD4+ T cells from gut-associated lymphoid tissue (GALT). Although the administration of antiretroviral therapy (ART) has been shown to increase CD4+ T-cell levels in the peripheral blood in both SIV and HIV infections, its efficacy in restoring intestinal mucosal CD4+ T cells has not been well investigated. To gain insights into the molecular mechanisms of virally induced disruptions in the mucosal immune system, we have evaluated longitudinal changes in viral burden, T-cell subsets, and mucosal gene expression profiles in SIV-infected rhesus macaques in the absence or presence of ART. Our results demonstrate a dramatic suppression of mucosal viral loads and rapid reconstitution of CD4+ T cells in GALT in animals receiving ART that were not observed in untreated SIV-infected animals. DNA microarray-based gene expression profiling indicated that CD4+ T-cell restoration in GALT was associated with up regulation of growth factors and genes involved in repair and regeneration of the mucosal epithelium. In contrast, untreated SIV-infected animals increased expression of lymphocyte activation and inflammatory response-associated genes and did not up regulate mucosal growth and repair associated transcription. In conclusion, these data indicate that initiating ART in primary SIV infection may lead to the restoration of the mucosal immune system through reduction of inflammation and promotion of epithelial repair in the intestinal mucosa.

scholarly journals Nfat

2002 ◽  
Vol 156 (5) ◽  
pp. 771-774 ◽  
Author(s):  
Valerie Horsley ◽  
Grace K. Pavlath
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factors ◽  
Immune System ◽  
Cell Types ◽  
Cytokine Gene Expression ◽  
Nuclear Factor ◽  
Cytokine Gene ◽  
Activated T Cells ◽  
Control Of Gene Expression

The nuclear factor of activated T cells (NFAT) proteins are a family of transcription factors whose activation is controlled by calcineurin, a Ca2+-dependent phosphatase. Originally identified in T cells as inducers of cytokine gene expression, NFAT proteins play varied roles in cells outside of the immune system. This review addresses the recent data implicating NFAT in the control of gene expression influencing the development and adaptation of numerous mammalian cell types.

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