TY - JOUR
T1 - Gemcitabine directly inhibits effector CD4 T cell activation and prevents experimental autoimmune encephalomyelitis
AU - Glenn, Justin D.
AU - Xue, Patrick
AU - Whartenby, Katharine A.
N1 - Funding Information:
This work was supported by the Maryland Stem Cell Research Fund , The National Multiple Sclerosis Society , (Research Grant RG1501027770 and Collaborative Center Grant), and the Silverman Foundation.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/3/15
Y1 - 2018/3/15
N2 - Pro-inflammatory T cells are critical to the pathogenesis of multiple sclerosis (MS). We investigated the potential for the anti-proliferative, pro-apoptotic drug gemcitabine to affect development of MS-relevant effector TH1, TH17, and Treg cells. Gemcitabine directly suppressed proliferation, activation, and induced apoptosis of all effector subsets in subtype and dose-dependent fashion. This drug also prevented development of disease in the MS model experimental autoimmune encephalomyelitis (EAE) and significantly reduced the abundance of TH1 and TH17 cells. Our results indicate that pathogenic CD4+ T cells may be viable targets by gemcitabine for therapeutic benefit in MS.
AB - Pro-inflammatory T cells are critical to the pathogenesis of multiple sclerosis (MS). We investigated the potential for the anti-proliferative, pro-apoptotic drug gemcitabine to affect development of MS-relevant effector TH1, TH17, and Treg cells. Gemcitabine directly suppressed proliferation, activation, and induced apoptosis of all effector subsets in subtype and dose-dependent fashion. This drug also prevented development of disease in the MS model experimental autoimmune encephalomyelitis (EAE) and significantly reduced the abundance of TH1 and TH17 cells. Our results indicate that pathogenic CD4+ T cells may be viable targets by gemcitabine for therapeutic benefit in MS.
KW - Experimental autoimmune encephalomyelitis
KW - Multiple sclerosis
KW - Neuro-inflammation
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=85038886553&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038886553&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2017.12.002
DO - 10.1016/j.jneuroim.2017.12.002
M3 - Article
C2 - 29274729
AN - SCOPUS:85038886553
SN - 0165-5728
VL - 316
SP - 7
EP - 16
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
ER -