Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice

Nicole L. Regna, Miranda D. Vieson, Xin M. Luo, Cristen B. Chafin, Abdul Gafoor Puthiyaveetil, Sarah E. Hammond, David L. Caudell, Matthew B. Jarpe, Christopher M. Reilly

Research output: Contribution to journalArticlepeer-review

Abstract

We sought to determine if a selective HDAC6 inhibitor (ACY-738) decreases disease in NZB/W mice. From 22 to 38weeks-of-age, mice were injected intraperitoneally with 5 or 20mg/kg of ACY-738, or vehicle control. Body weight and proteinuria were measured every 2weeks, while sera anti-dsDNA, Ig isotypes, and cytokine levels were measured every 4weeks. Kidney disease was determined by evaluation of sera, urine, immune complex deposition, and renal pathology. Flow cytometric analysis assessed thymic, splenic, bone marrow, and peripheral lymphocyte differentiation patterns. Our results showed HDAC6 inhibition decreased SLE disease by inhibiting immune complex-mediated glomerulonephritis, sera anti-dsDNA levels, and inflammatory cytokine production and increasing splenic Treg cells. Inhibition of HDAC6 increased the percentage of cells in the early-stage developmental fractions of both pro- and pre-B cells. These results suggest that specific HDAC6 inhibition may be able to decrease SLE disease by altering aberrant T and B cell differentiation.

Original languageEnglish (US)
Pages (from-to)58-73
Number of pages16
JournalClinical Immunology
Volume162
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • B cells
  • HDAC
  • Systemic lupus erythematosus
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice'. Together they form a unique fingerprint.

Cite this