The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance.
Antigen-presenting cells (APCs) induce T cell activation as well as T cell tolerance. The molecular basis of the regulation of this critical 'decision' is not well understood. Here we show that HDAC11, a member of the HDAC histone deacetylase family with no prior defined physiological function, negatively regulated expression of the gene encoding interleukin 10 (IL-10) in APCs. Overexpression of HDAC11 inhibited IL-10 expression and induced inflammatory APCs that were able to prime naive T cells and restore the responsiveness of tolerant CD4+ T cells. Conversely, disruption of HDAC11 in APCs led to upregulation of expression of the gene encoding IL-10 and impairment of antigen-specific T cell responses. Thus, HDAC11 represents a molecular target that influences immune activation versus immune tolerance, a critical 'decision' with substantial implications in autoimmunity, transplantation and cancer immunotherapy.
Villagra
Alejandro
A
Division of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Cheng
Fengdong
F
Wang
Hong-Wei
HW
Suarez
Ildelfonso
I
Glozak
Michelle
M
Maurin
Michelle
M
Nguyen
Danny
D
Wright
Kenneth L
KL
Atadja
Peter W
PW
Bhalla
Kapil
K
Pinilla-Ibarz
Javier
J
Seto
Edward
E
Sotomayor
Eduardo M
EM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D016753:Interleukin-10; C462506:HDAC11 protein, human; C528111:Hdac11 protein, mouse; D006655:Histone Deacetylases