Transcriptional Profiling of Th2 Cells Identifies Pathogenic Features Associated with Asthma.
Allergic asthma and rhinitis are two common chronic allergic diseases that affect the lungs and nose, respectively. Both diseases share clinical and pathological features characteristic of excessive allergen-induced type 2 inflammation, orchestrated by memory CD4(+) T cells that produce type 2 cytokines (Th2 cells). However, a large majority of subjects with allergic rhinitis do not develop asthma, suggesting divergence in disease mechanisms. Because Th2 cells play a pathogenic role in both these diseases and are also present in healthy nonallergic subjects, we performed global transcriptional profiling to determine whether there are qualitative differences in Th2 cells from subjects with allergic asthma, rhinitis, and healthy controls. Th2 cells from asthmatic subjects expressed higher levels of several genes that promote their survival as well as alter their metabolic pathways to favor persistence at sites of allergic inflammation. In addition, genes that enhanced Th2 polarization and Th2 cytokine production were also upregulated in asthma. Several genes that oppose T cell activation were downregulated in asthma, suggesting enhanced activation potential of Th2 cells from asthmatic subjects. Many novel genes with poorly defined functions were also differentially expressed in asthma. Thus, our transcriptomic analysis of circulating Th2 cells has identified several molecules that are likely to confer pathogenic features to Th2 cells that are either unique or common to both asthma and rhinitis.
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Grégory
0000-0002-8164-6852
G
Seumois
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Jose
0000-0002-9098-1652
J
Zapardiel-Gonzalo
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Brandie
B
White
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Divya
0000-0002-2961-735X
D
Singh
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Veronique
V
Schulten
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Myles
M
Dillon
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Denize
D
Hinz
Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093; and.
David H
DH
Broide
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
Alessandro
0000-0001-7013-2250
A
Sette
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; vijay@lji.org bpeters@lji.org.
Bjoern
B
Peters
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Clinical and Experimental Sciences, National Institute for Health Research Southampton Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton SO16 6YD, United Kingdom vijay@lji.org bpeters@lji.org.
Pandurangan
P
Vijayanand
D001249:Asthma / Q000235:genetics / Q000276:immunology*; D002469:Cell Separation; D058501:Enzyme-Linked Immunospot Assay; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D065631:Rhinitis, Allergic / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D059467:Transcriptome / Q000276:immunology*