Theranostics 2018; 8(11):2927-2938. doi:10.7150/thno.25317
Histone deacetylase 6 modulates macrophage infiltration during inflammation
1. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China.
2. Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
3. Department of Pathology, Harvard Medical School and Department of Lab Medicine, Children's Hospital Boston and Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
*These authors contributed equally to this work.
Mice with histone deacetylase 6 (HDAC6) deficiency grow and develop normally but exhibit impaired immune response. The molecular mechanisms for this phenotype remain largely elusive.
Methods: A mouse acute peritonitis model was used to study the infiltration of neutrophils and monocyte-derived macrophages. In vitro cell motility assays were performed to analyze monocyte/macrophage recruitment. Fluorescence microscopy and flow cytometry were performed to examine the phagocytic ability of macrophages. Immunofluorescence microscopy was used to investigate protein localization, protrusion formation, and microtubule acetylation.
Results: HDAC6 deficiency does not affect neutrophil infiltration, but instead attenuates the infiltration of monocyte-derived macrophages into the peritoneal cavity. HDAC6 plays a specific role in monocyte/macrophage recruitment. Loss of HDAC6 suppresses the phagocytic capacity of macrophages challenged with E. coli. Lipopolysaccharide stimulation results in the translocation of HDAC6 and cortactin from the cytosol to the cell periphery, promotes the formation of filopodial protrusions, and enhances microtubule acetylation around the microtubule-organizing center, all of which are abrogated by HDAC6 deficiency.
Conclusion: These findings implicate HDAC6 in the innate immune response and suggest that it may serve as a promising target for the treatment of macrophage-associated immune diseases.
Keywords: HDAC6, inflammation, macrophage, infiltration, migration, acetylation
Yan B, Xie S, Liu Y, Liu W, Li D, Liu M, Luo HR, Zhou J. Histone deacetylase 6 modulates macrophage infiltration during inflammation. Theranostics 2018; 8(11):2927-2938. doi:10.7150/thno.25317. Available from http://www.thno.org/v08p2927.htm