T-cell regulation in asthmatic diseases.
Effector and regulatory T cells (Tregs) play a fundamental role in the airways in allergic asthma. Here, the role of T cells in the immunopathogenesis of human asthma as well as in animal models of allergic airway inflammation is reviewed. Recent data have shown that Th2 and Th17 effector T cells augment experimental airway inflammation, while Tregs have an important anti-inflammatory function. The local induction of Th2 cells is critically dependent on the balance between the transcription factors T-bet and GATA-3, while Th17 and Tregs require the transcription factors ROR-gammat and Foxp3, respectively. Cytokine signaling controls the development and activation of all the above T-cell subsets. For instance, local blockade of the membrane-bound interleukin (IL)-6R results in induction of lung CD4+CD25+ Foxp3+Tregs producing TGF-Beta and IL-10. In humans, it has been suggested that asthmatic patients have increased Th2 but decreased Tregs, however the role of Th17 cells in allergic asthma remains to be elucidated. However, the currently available data suggest that allergic asthma is a multifaceted disease that is actively controlled by T lymphocytes. A better understanding of effector and Treg activation will most likely lead to novel treatment strategies in the near future.
Finotto
S
S
Laboratory of Cellular and Molecular Lung Immunology, First Medical Clinic, Mainz, Germany.
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D025461:Feedback, Physiological / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D050980:GATA Transcription Factors / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000276:immunology; D011988:Receptors, Thyroid Hormone / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D000098815:T-bet Transcription Factor
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050980:GATA Transcription Factors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor