Page 112 - Read Online

Page 180 Muroy et al. Neuroimmunol Neuroinflammation 2020;7:166-82 I http://dx.doi.org/10.20517/2347-8659.2020.16

Altogether, our results show that Phf15 is a novel repressor of microglial inflammatory gene expression,
regulating both the magnitude and time-to-resolution of the inflammatory response. Importantly, Phf15
also serves to repress baseline inflammatory output in the absence of immune activation. Putatively,
increases in Phf15 during healthy aging could help counteract brain inflammation and protect brain health.

Future studies will determine the mechanism of action of Phf15. For example, the identity of its binding
partner proteins and its genome-wide binding sites and associated histone marks will be elucidated to
determine the specific gene regulatory regions it interacts with (e.g., active enhancers or promoters).
Additionally, studies in Phf15 KO mice will determine whether loss of Phf15-mediated repression of
proinflammatory factors is sufficient to induce cognitive decline or exacerbate LPS-induced neurotoxicity
of dopaminergic neurons in the substantia nigra.

DECLARATIONS
Acknowledgments
We thank Prof. Ellen Robey for helpful comments on the manuscript and Wendy Yan for technical
assistance.

Authors’ contributions
Designed and performed experiments, analyzed data, and wrote the manuscript: Muroy SE
Performed experiments and analyzed data: Timblin GA, Preininger MK
Performed experiments: Cedillo P
Designed experiments and wrote the manuscript: Saijo K

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by the Berkeley Fellowship to S.E.M., ADA Postdoctoral fellowship to G.A.T.,
NSF GRFP to M.K.P., and R01HD092093 and Pew Scholarship to K.S.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
All procedures were approved by the Animal Care and Use Committee of the University of California,
Berkeley (Animal Use Protocol AUP-2017-02-9539).

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

REFERENCES
1. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev 2011;91:461-553.
2. Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.
Science 2005;308:1314-8.
3. Parkhurst CN, Gan WB. Microglia dynamics and function in the CNS. Curr Opin Neurobiol 2010;20:595-600.
4. Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Ann Rev Immunol 2009;27:119-45.
5. Saijo K, Glass CK. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol 2011;11:775-87.