Roles of histone hypoacetylation in LAT expression on T cells and Th2 polarization in allergic asthma.
BACKGROUND
Linker for activation of T cells (LAT), a transmembrane adaptor protein, plays a role in T cell and mast cell function, while it remains unclear how histone modifications mediate LAT expression in allergic asthma. The present study aimed at understanding alterations of lymphocyte LAT in patients with asthma and potential mechanisms by which histone modulation may be involved in.


METHODS
The expression of LAT mRNA was checked by Quantitative real-time PCR and histone hypoacetylation on LAT promoter was detected by Chromatin Immunoprecipitation.


RESULTS
Our results demonstrated that the expression of LAT mRNA in peripheral blood T cells from patients with asthma decreased, as compared to healthy controls. Peripheral blood T cells were treated with pCMV-myc-LAT, pCMV-myc or LAT-siRNA plasmid. Over-expression of LAT mRNA and decrease of Th2 cytokine production were noted, which could be prevented by the inhibition of LAT. The further investigation of the role of histone was performed in an asthma model induced by allergen. Histone hypoacetylation on LAT promoter could inhibit LAT expression and enhanced Th2 differentiation, while trichostatin A, a histone deacetylase inhibitor, promoted LAT expression and inhibited Th2 cytokine production.


CONCLUSIONS
Our results indicate that histone hypoacetylation may regulate LAT expression on T cells and modify Th2 polarization in allergic asthma.
Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.
Cheng-ye
CY
Li
Juan
J
Peng
Lian-pin
LP
Ren
Li-xing
LX
Gan
Xiao-jiong
XJ
Lu
Qian
Q
Liu
Wen
W
Gu
Xue-jun
XJ
Guo
D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D006657:Histones; C110810:LAT protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma