Thymic stromal lymphopoietin induction by skin irritation is independent of tumour necrosis factor-α, but supported by interleukin-1

Kumari, Vandana; Babina, Magda; Hazzan, Tarek; Worm, Margitta

doi:10.1111/bjd.13465

Cited by 23 publications

(29 citation statements)

References 72 publications

(145 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This will induce production of pro‐inflammatory stimuli or alarmins which act as a danger signal for the activation of innate immune cells and release of chemokines and cytokines . Kumari et al showed recently that acute barrier disruption by physical or chemical perturbation may be sufficient to initiate thymic stromal lymphopoietin (TSLP) responses in the skin, and that this process was coordinated by endogenous alarmins including IL‐1α. The innate response is rapid and, in the case of strong irritants like acids, bases and some solvents, occurs shortly after exposure on the exposed skin sites.…”

Section: Immune Activationmentioning

confidence: 99%

“…In this regard, SC is unique as it acts as a reservoir of preformed biologically active IL‐1α . Upon skin barrier damage, IL‐1α is released from a preformed pool into the intercellular space leading to activation of several distinct signalling pathways and upregulation of the expression of secondary cytokines, adhesion molecules, chemokines, which are potent chemoattractants for leucocytes and may induce T‐cell activation independent of exogenous antigen ultimately leading to ICD . Of note, the interaction of the skin barrier and immune response is not unidirectional.…”

Section: The Normal Skin Barriermentioning

confidence: 99%

See 1 more Smart Citation

The role of skin barrier in occupational contact dermatitis

Jakaša

Thyssen

Kežić

2018

Experimental Dermatology

View full text Add to dashboard Cite

Skin diseases represent one of the most common work-related diseases and may have a detrimental effect on social, personal and occupational aspects of life. Contact dermatitis (CD), which comprises predominately irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD), accounts for vast majority of occupational skin diseases, especially in occupations associated with frequent skin contact with irritants and contact allergens. Although ICD and ACD have similar clinical manifestation, their pathophysiology and the role of the skin barrier are different. In ICD, perturbation of the skin barrier is the primary event which sets into motion diverse metabolic processes and triggers activation of innate immunity without the involvement of adaptive immune system. In ACD, a type IV hypersensitivity reaction induced by contact allergens, the skin barrier impairment may evoke innate signalling pathways during the sensitization phase required for the activation of T-cell adaptive response. Thus, skin barrier impairment may increase the risk of ICD or ACD not only because of enhanced permeability and ingress of irritants and allergens but also by the generation of innate immune signal needed for the induction of allergic response. Hence, an efficient way to prevent CD is to avoid skin barrier damage in the workplace. This review focuses on the skin barrier, how it is affected by skin irritants and how its impairment contributes to the development of ICD and ACD.

show abstract

Section: Immune Activationmentioning

confidence: 99%

Section: The Normal Skin Barriermentioning

confidence: 99%

The role of skin barrier in occupational contact dermatitis

Jakaša

Thyssen

Kežić

2018

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…TSLP is highly expressed in KCs when the skin barrier is compromised by genetic manipulation . Likewise, irritation‐mediated barrier disruption elicits TSLP responses, providing a further link between defective skin integrity and TSLP expression . TSLP can thus be viewed as an early and sensitive indicator of skin perturbation of various sorts, making it essential to elucidate the molecular underpinnings of its regulation.…”

Section: Discussionmentioning

confidence: 99%

“…Befitting its essential role in skin inflammation, IL‐1 contributed to the induction of TSLP in irritated skin, yet could provide a partial explanation only, as interference resulted in 20–50% inhibition, depending on the system . We therefore asked in the present study what alternative routes may be triggered in the perturbed skin to promote TSLP.…”

Section: Discussionmentioning

confidence: 99%

Thymic stromal lymphopoietin production induced by skin irritation results from concomitant activation of protease‐activated receptor 2 and interleukin 1 pathways

et al. 2019

Self Cite

View full text Add to dashboard Cite

Summary Background Thymic stromal lymphopoietin (TSLP) mediates proallergic T helper 2‐type responses by acting on leucocytes. Endogenous pathways regulating TSLP production are poorly defined. Objectives To uncover the mechanisms by which skin barrier disruption elicits TSLP production and to delineate the level at which individual mechanistic components may converge. Methods A combination of primary keratinocytes, skin explants and in vivo strategies was employed. Murine skin was tape stripped in the presence of neutralizing antibodies or antagonists. Cells and explants were stimulated with interleukin (IL)‐1 and protease‐activated receptor 2 agonist (PAR‐2‐Ag). TSLP levels were quantified by enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction. Chromatin immunoprecipitation and promoter reporter assays were used to examine recruitment and functional activity of nuclear factor kappa B (NF‐κB) at the TSLP promoter. Results TSLP induction in mouse skin occurred in a PAR‐2‐ and IL‐1‐dependent manner. This scenario was duplicated by exogenous IL‐1 plus PAR‐2‐Ag vs. each stimulus alone. Joint activity of PAR‐2 and IL‐1 was also observed in human keratinocytes. The TSLP promoter was identified as the target of PAR‐2/IL‐1, whereby PAR‐2 activation augmented the recruitment of NF‐κB and transcriptional activation over IL‐1 alone. Combined treatment showed activity at concentrations of IL‐1 unable to elicit NF‐κB activity on their own. Conclusions Skin barrier disruption activates the IL‐1 and the PAR‐2 pathways, which act in concert to activate the TSLP promoter and possibly other inflammatory genes. Awareness of this combined activity may permit a more flexible clinical management by selective targeting of either pathway individually or collectively. What's already known about this topic? Thymic stromal lymphopoietin (TSLP) is rapidly induced upon skin perturbation and mediates proallergic T helper 2‐type responses by acting on leucocytes. Endogenous control of TSLP expression is poorly understood, but interleukin (IL)‐1 is one regulator in the cutaneous environment In addition to IL‐1, protease‐activated receptor 2 (PAR‐2) organizes central inflammatory pathways in the skin. What does this study add? IL‐1 and PAR‐2 pathways cooperate in driving TSLP production in mice and humans. Pathway integration occurs at the level of the TSLP promoter through enhanced recruitment and transcriptional activation of nuclear factor kappa B. When PAR‐2 is co‐stimulated, very low IL‐1 levels (inactive by themselves) can induce biologically meaningful responses in the skin environment. What is the translational message? Physical skin irritation results in robust TSLP production by simultaneous activation of PAR‐2 and IL‐1 pathways.

show abstract

“…In this issue of the BJD Kumari et al . have focused on the potential role of physico‐chemical irritation of the skin as triggering factors for TSLP induction, as well as differences in the role of tumour necrosis factor (TNF)‐α and IL‐1 in the context of TSLP production in murine and human skin.…”

Section: Funding Sourcesmentioning

confidence: 99%

Exploring the biological mechanisms of thymic stromal lymphopoietin

Sonesson

2015

Br J Dermatol

View full text Add to dashboard Cite

Thymic stromal lymphopoietin induction by skin irritation is independent of tumour necrosis factor-α, but supported by interleukin-1

Cited by 23 publications

References 72 publications

The role of skin barrier in occupational contact dermatitis

The role of skin barrier in occupational contact dermatitis

Thymic stromal lymphopoietin production induced by skin irritation results from concomitant activation of protease‐activated receptor 2 and interleukin 1 pathways

Exploring the biological mechanisms of thymic stromal lymphopoietin

Contact Info

Product

Resources

About