Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte Activation

作者：Navabi Nazanin; Whitt Jordan; Wu Shu en; Woo Vivienne; Moncivaiz Jessica; Jordan Michael B; Vallance Bruce A; Way Sing Sing; Alenghat Theresa

来源：Cell Reports, 2017, 19(6): 1165-1175.

DOI：10.1016/j.celrep.2017.04.046

Mucosal tissues are constantly in direct contact with diverse beneficial and pathogenic microbes, highlighting the need for orchestrating complex microbial signals to sustain effective host defense. Here, we show an essential role for intestinal epithelial cell expression of histone deacetylase 3 (HDAC3) in responding to pathogenic microbes and activating protective innate immunity. Mice lacking HDAC3 in intestinal epithelial cells were more susceptible to Citrobacter rodentium when under tonic stimulation by the commensal microbiota. This impaired host defense reflected significantly decreased IFN gamma production by intraepithelial CD8(+) T cells early during infection. Further, HDAC3 was necessary for infection-induced epithelial expression of the IFN gamma-inducing factor IL-18, and administration of IL-18 restored IFN gamma activity to resident CD8(+) T cells and reduced infection. Thus, HDAC3 mediates communication between intestinal epithelial cells and resident lymphocytes, revealing that epithelial priming by an epigenetic modifier may direct mucosal regulation of host defense against pathogenic microbes.

• 出版日期2017-5-9