Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells

DSpace/Manakin Repository

Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells

Citable link to this page

 

 
Title: Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells
Author: Fu, Wenxian; Farache, Julia; Clardy, Susan M; Hattori, Kimie; Mander, Palwinder; Lee, Kevin; Rioja, Inmaculada; Weissleder, Ralph; Prinjha, Rab K; Benoist, Christophe; Mathis, Diane

Note: Order does not necessarily reflect citation order of authors.

Citation: Fu, W., J. Farache, S. M. Clardy, K. Hattori, P. Mander, K. Lee, I. Rioja, et al. 2014. “Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells.” eLife 3 (1): e04631. doi:10.7554/eLife.04631. http://dx.doi.org/10.7554/eLife.04631.
Full Text & Related Files:
Abstract: Epigenetic modifiers are an emerging class of anti-tumor drugs, potent in multiple cancer contexts. Their effect on spontaneously developing autoimmune diseases has been little explored. We report that a short treatment with I-BET151, a small-molecule inhibitor of a family of bromodomain-containing transcriptional regulators, irreversibly suppressed development of type-1 diabetes in NOD mice. The inhibitor could prevent or clear insulitis, but had minimal influence on the transcriptomes of infiltrating and circulating T cells. Rather, it induced pancreatic macrophages to adopt an anti-inflammatory phenotype, impacting the NF-κB pathway in particular. I-BET151 also elicited regeneration of islet β-cells, inducing proliferation and expression of genes encoding transcription factors key to β-cell differentiation/function. The effect on β cells did not require T cell infiltration of the islets. Thus, treatment with I-BET151 achieves a ‘combination therapy’ currently advocated by many diabetes investigators, operating by a novel mechanism that coincidentally dampens islet inflammation and enhances β-cell regeneration. DOI: http://dx.doi.org/10.7554/eLife.04631.001
Published Version: doi:10.7554/eLife.04631
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270084/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13890767
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters