Dataset Information

Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung.

ABSTRACT:

Background

Allergic asthma results from inappropriate T(H)2-mediated inflammation. Both IL-4 and IL-13 contribute to asthma pathogenesis, but IL-4 predominantly drives T(H)2 induction, whereas IL-13 is necessary and sufficient for allergen-induced airway hyperresponsiveness and goblet cell hyperplasia. Although these 2 cytokines share signaling components, the molecular mechanisms by which they mediate different phases of the allergic asthmatic response remain elusive.

Objective

We sought to clarify the role or roles of IL-4 and IL-13 in asthma-pathogenesis.

Methods

We used DNA Affymetrix microarrays to profile pulmonary gene expression in BALB/c mice inoculated intratracheally with ragweed pollen, house dust mite, IL-4, IL-13, or both cytokines. IL-13 dependence was confirmed by comparing pulmonary gene expression in house dust mite-inoculated wild-type and IL-13 knockout mice.

Results

A signature gene expression profile consisting of 23 genes was commonly induced by means of inoculation with house dust mite, ragweed pollen, or IL-4 plus IL-13. Although rIL-4 and rIL-13 treatment induced an overlapping set of genes, IL-4 uniquely induced 21 genes, half of which were interferon response genes and half of which were genes important in immunoregulation. IL-13 uniquely induced 8 genes, most of which encode proteins produced by epithelial cells.

Conclusions

IL-4 and IL-13 together account for most allergen-induced pulmonary genes. Selective IL-4 induction of IFN-gamma response genes and other genes that might negatively regulate allergic inflammation could partially explain the greater importance of IL-13 in the effector phase of allergic airway disease.

SUBMITTER: Lewis CC

PROVIDER: S-EPMC2766779 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Publications

Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung.

Lewis Christina C CC Aronow Bruce B Hutton John J Santeliz Joanna J Dienger Krista K Herman Nancy N Finkelman Fred D FD Wills-Karp Marsha M

The Journal of allergy and clinical immunology 20090226 4

<h4>Background</h4>Allergic asthma results from inappropriate T(H)2-mediated inflammation. Both IL-4 and IL-13 contribute to asthma pathogenesis, but IL-4 predominantly drives T(H)2 induction, whereas IL-13 is necessary and sufficient for allergen-induced airway hyperresponsiveness and goblet cell hyperplasia. Although these 2 cytokines share signaling components, the molecular mechanisms by which they mediate different phases of the allergic asthmatic response remain elusive.<h4>Objective</h4>W ...[more]

PMID: 19249085

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Project description:Background:The immune cells in the local environments surrounding non-small cell lung cancer (NSCLC) implicate the balance of pro- and antitumor immunity; however, their transcriptomic profiles remain poorly understood. Methods:A transcriptomic microarray study of bronchoalveolar lavage (BAL) cells harvested from tumor-bearing lung segments was performed in a discovery group. The findings were validated (1) in published microarray datasets, (2) in an independent group by RT-qPCR, and (3) in non-diseased and tumor adjacent non-neoplastic lung tissue by immunohistochemistry and in BAL cell lysates by immunoblotting. Result:The differential expression of 129 genes was identified in the discovery group. These genes revealed functional enrichment in Fc gamma receptor-dependent phagocytosis and circulating immunoglobulin complex among others. Microarray datasets analysis (n?=?607) showed that gene expression of BAL cells of tumor-bearing lung segment was also the unique transcriptomic profile of tumor adjacent non-neoplastic lung of early stage NSCLC and a significantly gradient increase of immunoglobulin genes' expression for non-diseased lungs, tumor adjacent non-neoplastic lungs, and tumors was identified (ANOVA, p?<?2?×?10-16). A 53-gene signature was determined with significant correlation with inhibitory checkpoint PDCD1 (r?=?0.59, p?=?0.0078) among others, where the nine top genes including IGJ and IGKC were RT-qPCR validated with high diagnostic performance (AUC: 0.920, 95% CI: 0.831-0.985, p?=?2.98?×?10-7). Increased staining and expression of IGKC revealed by immunohistochemistry and immunoblotting in tumor adjacent non-neoplastic lung tissues (Wilcoxon signed-rank test, p?<?0.001) and in BAL cell lysates (p?<?0.01) of NSCLC, respectively, were noted. Conclusion:The BAL cells of tumor-bearing lung segments and tumor adjacent non-neoplastic lung tissues present a unique gene expression characterized by IGKC in relation to inhibitory checkpoints. Further study of humoral immune responses to NSCLC is warranted.

Dataset Information

Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung.

Background

Objective

Methods

Results

Conclusions

Publications

Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung.

Similar Datasets

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