Cutting Edge: An Inactive Chromatin Configuration at the IL-10 Locus in Human Neutrophils

To identify the molecular basis of IL-10 expression in human phagocytes, we evaluated the chromatin modifica-tion status at their genomic locus. We analyzedposttranslational modifications of histones associatedwith genes that are active, repressed, or poised for tran-scriptional activation, including H3K4me3, H4Ac,H3K27Ac, and H3K4me1 marks. Differently from au-tologous IL-10–producing monocytes, none of the marksunder evaluation was detected at the locus of rest-ing or activated neutrophils from healthy subjects ormelanoma patients. By contrast, increased H3K4me3,H4Ac, H3K4me1, and H3K27Ac levels were detectedat syntenic regions of the locus in mouse neutro-phils. Altogether, data demonstrate that human neutro-phils, differently from either monocytes or mouseneutrophils, cannot switch on the gene becauseits locus is in an inactive state, likely reflecting a neutro-phil-specific developmental outcome. Implicitly, dataalso definitively settle a currently unsolved issue on thecapacity of human neutrophils to produce IL-10.