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Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma.
J Allergy Clin Immunol. 2012 Jan; 129(1):104-11.e1-9.JA

Abstract

BACKGROUND

Thymic stromal lymphopoietin (TSLP) is a cytokine implicated in the pathophysiology of asthma through 2 distinct pathways: a TSLP-OX40 ligand (OX40L)-T cell axis and a TSLP-mast cell axis. Whether these pathways are active in human asthma is unknown.

OBJECTIVE

We sought to investigate whether mucosal TSLP protein expression relates to asthma severity and distinct immunologic pathways.

METHODS

In healthy subjects and patients with mild-to-severe asthma, we immunostained bronchial biopsy specimens for TSLP, OX40, OX40L, T(H)2 cytokines, and inflammatory cell markers. We examined gene expression using RNA microarrays and quantitative RT-PCR.

RESULTS

There was considerable heterogeneity in the levels of TSLP, IL-13, and IL-4 immunostaining across the cohort of asthmatic patients examined. Overall, TSLP protein expression was significantly increased in airway epithelium and lamina propria of asthmatic patients, particularly in patients with severe asthma. TSLP immunostaining in both compartments correlated with the severity of airflow obstruction. The majority of leukocytes expressing IL-13 were possibly nuocytes. Accounting for intersubject variability, the 55% of asthmatic patients with increased IL-13 immunostaining in the lamina propria also had increased IL-4 and TSLP expression. This was further substantiated by significant correlations between TSLP gene expression, a T(H)2 gene expression signature, and eosinophilic inflammation in bronchial biopsy specimens. Immunostaining for OX40, OX40L, and CD83 was sparse, with no difference between asthmatic patients and healthy subjects.

CONCLUSION

TSLP expression is increased in a subset of patients with severe asthma in spite of high-dose inhaled or oral corticosteroid therapy. Targeting TSLP might only be efficacious in the subset of asthma characterized by increased TSLP expression and T(H)2 inflammation.

Authors+Show Affiliations

Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21975173

Citation

Shikotra, Aarti, et al. "Increased Expression of Immunoreactive Thymic Stromal Lymphopoietin in Patients With Severe Asthma." The Journal of Allergy and Clinical Immunology, vol. 129, no. 1, 2012, pp. 104-11.e1-9.
Shikotra A, Choy DF, Ohri CM, et al. Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. J Allergy Clin Immunol. 2012;129(1):104-11.e1-9.
Shikotra, A., Choy, D. F., Ohri, C. M., Doran, E., Butler, C., Hargadon, B., Shelley, M., Abbas, A. R., Austin, C. D., Jackman, J., Wu, L. C., Heaney, L. G., Arron, J. R., & Bradding, P. (2012). Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. The Journal of Allergy and Clinical Immunology, 129(1), 104-e1-9. https://doi.org/10.1016/j.jaci.2011.08.031
Shikotra A, et al. Increased Expression of Immunoreactive Thymic Stromal Lymphopoietin in Patients With Severe Asthma. J Allergy Clin Immunol. 2012;129(1):104-11.e1-9. PubMed PMID: 21975173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. AU - Shikotra,Aarti, AU - Choy,David F, AU - Ohri,Chandra M, AU - Doran,Emma, AU - Butler,Claire, AU - Hargadon,Beverley, AU - Shelley,Maria, AU - Abbas,Alexander R, AU - Austin,Cary D, AU - Jackman,Janet, AU - Wu,Lawren C, AU - Heaney,Liam G, AU - Arron,Joseph R, AU - Bradding,Peter, Y1 - 2011/10/05/ PY - 2011/03/16/received PY - 2011/08/02/revised PY - 2011/08/29/accepted PY - 2011/10/7/entrez PY - 2011/10/7/pubmed PY - 2012/7/4/medline SP - 104-11.e1-9 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 129 IS - 1 N2 - BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a cytokine implicated in the pathophysiology of asthma through 2 distinct pathways: a TSLP-OX40 ligand (OX40L)-T cell axis and a TSLP-mast cell axis. Whether these pathways are active in human asthma is unknown. OBJECTIVE: We sought to investigate whether mucosal TSLP protein expression relates to asthma severity and distinct immunologic pathways. METHODS: In healthy subjects and patients with mild-to-severe asthma, we immunostained bronchial biopsy specimens for TSLP, OX40, OX40L, T(H)2 cytokines, and inflammatory cell markers. We examined gene expression using RNA microarrays and quantitative RT-PCR. RESULTS: There was considerable heterogeneity in the levels of TSLP, IL-13, and IL-4 immunostaining across the cohort of asthmatic patients examined. Overall, TSLP protein expression was significantly increased in airway epithelium and lamina propria of asthmatic patients, particularly in patients with severe asthma. TSLP immunostaining in both compartments correlated with the severity of airflow obstruction. The majority of leukocytes expressing IL-13 were possibly nuocytes. Accounting for intersubject variability, the 55% of asthmatic patients with increased IL-13 immunostaining in the lamina propria also had increased IL-4 and TSLP expression. This was further substantiated by significant correlations between TSLP gene expression, a T(H)2 gene expression signature, and eosinophilic inflammation in bronchial biopsy specimens. Immunostaining for OX40, OX40L, and CD83 was sparse, with no difference between asthmatic patients and healthy subjects. CONCLUSION: TSLP expression is increased in a subset of patients with severe asthma in spite of high-dose inhaled or oral corticosteroid therapy. Targeting TSLP might only be efficacious in the subset of asthma characterized by increased TSLP expression and T(H)2 inflammation. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/21975173/Increased_expression_of_immunoreactive_thymic_stromal_lymphopoietin_in_patients_with_severe_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(11)01397-2 DB - PRIME DP - Unbound Medicine ER -