Dataset Information

Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression.

ABSTRACT:

Background

Atopic dermatitis is characterized by scratching and by T(H)2-dominated immune response to cutaneously introduced antigens. Antigen application to skin mechanically injured by tape stripping results in T(H)2-dominated skin inflammation.

Objective

To examine the effect of tape stripping on the capacity of skin dendritic cells (DCs) to polarize T cells toward a T(H)2 phenotype.

Methods

CD11c(+) DCs were isolated from skin of BALB/c or C57BL/6 mice. Fluorescein isothiocyanate (FITC)(+) and FITC(-) DCs were isolated from draining lymph nodes (DLNs) 24 hours after painting the skin with FITC. DCs were assessed for their ability to induce cytokine secretion by ovalbumin-stimulated naive CD4(+) T cells from T cell receptor-ovalbumin transgenic DO11.10 mice. Cytokine mRNA levels were examined by quantitative PCR.

Results

Dendritic cells isolated from the skin of wild-type, but not thymic stromal lymphopoietin (TSLP) receptor(-/-) or IL-10(-/-), mice 6 hours after tape stripping elicited significantly more IL-4 and IL-13 and significantly less IFN-? production by CD4(+) cells than DCs isolated from unmanipulated skin, and expressed significantly more mRNA for the T(H)2 skewing molecules IL-10, Jagged1, and Jagged2, but significantly less mRNA for the T(H)1 skewing cytokine IL-12. CD11c(+)FITC(+) cells isolated from DLNs of shaved and tape stripped skin of wild-type, but not TSLP receptor(-/-) or IL-10(-/-), mice polarized T cells significantly more toward T(H)2 and expressed significantly more IL-10, Jagged1, and Jagged2 mRNA than CD11c(+)FITC(+) cells isolated from DLNs of shaved skin. Tape stripping significantly increased TSLP levels in the skin, and TSLP was shown to play an essential role in the T(H)2 polarization of skin DCs by tape stripping.

Conclusions

Tape stripping upregulates TSLP levels in the skin, which polarizes skin DCs to elicit a T(H)2 response via the induction of IL-10.

SUBMITTER: Oyoshi MK

PROVIDER: S-EPMC3085022 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression.

Oyoshi Michiko K MK Larson Ryan P RP Ziegler Steven F SF Geha Raif S RS

The Journal of allergy and clinical immunology 20101101 5

<h4>Background</h4>Atopic dermatitis is characterized by scratching and by T(H)2-dominated immune response to cutaneously introduced antigens. Antigen application to skin mechanically injured by tape stripping results in T(H)2-dominated skin inflammation.<h4>Objective</h4>To examine the effect of tape stripping on the capacity of skin dendritic cells (DCs) to polarize T cells toward a T(H)2 phenotype.<h4>Methods</h4>CD11c(+) DCs were isolated from skin of BALB/c or C57BL/6 mice. Fluorescein isot ...[more]

PMID: 21050944

Similar Datasets

Project description:Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine originally isolated from a murine thymic stromal cell line. TSLP exerts its biological effects by binding to a high-affinity heteromeric complex composed of thymic stromal lymphopoietin receptor chain and IL-7Rα. TSLP is primarily expressed by activated lung and intestinal epithelial cells, keratinocytes, and fibroblasts. However, dendritic cells (DCs), mast cells, and presumably other immune cells can also produce TSLP. Different groups of investigators have demonstrated the existence of two variants for TSLP in human tissues: the main isoform expressed in steady state is the short form (sf TSLP), which plays a homeostatic role, whereas the long form (lfTSLP) is upregulated in inflammatory conditions. In addition, there is evidence that in pathological conditions, TSLP can be cleaved by several endogenous proteases. Several cellular targets for TSLP have been identified, including immune (DCs, ILC2, T and B cells, NKT and Treg cells, eosinophils, neutrophils, basophils, monocytes, mast cells, and macrophages) and non-immune cells (platelets and sensory neurons). TSLP has been originally implicated in a variety of allergic diseases (e.g., atopic dermatitis, bronchial asthma, eosinophilic esophagitis). Emerging evidence indicates that TSLP is also involved in chronic inflammatory (i.e., chronic obstructive pulmonary disease and celiac disease) and autoimmune (e.g., psoriasis, rheumatoid arthritis) disorders and several cancers. These emerging observations greatly widen the role of TSLP in different human diseases. Most of these studies have not used tools to analyze the expression of the two TSLP isoforms. The broad pathophysiologic profile of TSLP has motivated therapeutic targeting of this cytokine. Tezepelumab is a first-in-class human monoclonal antibody (1) that binds to TSLP inhibiting its interaction with TSLP receptor complex. Tezepelumab given as an add-on-therapy to patients with severe uncontrolled asthma has shown safety and efficacy. Several clinical trials are evaluating the safety and the efficacy of tezepelumab in different inflammatory disorders. Monoclonal antibodies used to neutralize TSLP should not interact or hamper the homeostatic effects of sf TSLP.

Dataset Information

Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression.

Background

Objective

Methods

Results

Conclusions

Publications

Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression.

Similar Datasets

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