The activation and regulation of lymphocytes play a central role in asthmatic inflammation. It is increasingly recognized that diverse panels of lymphocyte lineages and cytokine profiles are involved in the asthmatic phenotypes. In this review, we discuss the advances in the gene variants associated with the regulation of lymphocytes and relevant cytokines underlying asthma and allergic diseases. We also discuss the current evidence about the epigenetic regulation of lymphocyte differentiation and the interaction with environment.
Many genetic variants in asthma are functionally associated with lymphocytes and relevant cytokines. Interleukin (IL)-2RB is important in the homeostasis of T regulatory cells (Tregs) through effects from IL-2. IL-18R1 and ST2/IL-1RL1 drive the T helper 1 and 2 inflammation via the ligands of their encoding receptors. Novel genes, like orosomucoid 1-like 3/gasdermin-like gene and taste receptor type 2 members are being explored for their roles in T-cell activation. T-cell lineages are epigenetically regulated by de novo methyltransferases, histone methylase, CD44 and microRNA. Environmental factors such as second-hand smoke and ambient air pollution modify Tregs differentiation significantly.
Plenty of genetic loci of lymphocyte regulation provide us a deeper insight into the asthma pathogenesis. Future challenge is to define genetic drivers in asthma phenotypes to provide therapeutic targets.
aMeakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada
bDepartment of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan
cRashid hospital DHA, University of Sharjah, , Sharjah, United Arab Emirates
Correspondence to Dr Qutayba Hamid, Meakins-Christie Laboratories, McGill University, 3626 Rue St-Urbain, Montreal, Quebec H2X 2P2, Canada. Tel: +1 514 398 38645 ext.00143; e-mail: firstname.lastname@example.org