2. Academic Validation
  3. Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice

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

  • Clin Immunol. 2016 Jan;162:58-73. doi: 10.1016/j.clim.2015.11.007.
Nicole L Regna 1,  Miranda D Vieson 1,  Xin M Luo 1,  Cristen B Chafin 1,  Abdul Gafoor Puthiyaveetil 2,  Sarah E Hammond 1,  David L Caudell 3,  Matthew B Jarpe 4,  Christopher M Reilly 5
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States.
  • 2 Department of Biotechnology, American University of Ras Al Khaimah, United Arab Emirates.
  • 3 Wake Forest University Primate Center, Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States.
  • 4 Acetylon Pharmaceuticals, Inc., 70 Fargo St., Boston, MA 02210, United States.
  • 5 Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States; Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060, United States. Electronic address: chreilly@vt.edu.
PMID: 26604012 DOI: 10.1016/j.clim.2015.11.007
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.

Keywords

B cells; HDAC; Systemic lupus erythematosus; T cells.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-19327
    99.92%, HDAC6 Inhibitor