TY - JOUR
T1 - Dendritic cells, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase and pulsed with a myelin antigen, provide myelin-specific suppression of ongoing experimental allergic encephalomyelitis
AU - Li, Chih Huang
AU - Zhang, Jintao
AU - Baylink, David J.
AU - Wang, Xiaohua
AU - Goparaju, Naga Bharani
AU - Xu, Yi
AU - Wasnik, Samiksha
AU - Cheng, Yanmei
AU - Berumen, Edmundo Carreon
AU - Qin, Xuezhong
AU - Lau, Kin Hing William
AU - Tang, Xiaolei
N1 - Publisher Copyright:
© FASEB.
PY - 2017/7
Y1 - 2017/7
N2 - Multiple sclerosis (MS) is caused by immune-mediated damage of myelin sheath. Current therapies aim to block such immune responses. However, this blocking is not sufficiently specific and hence compromises immunity, leading to severe side effects. In addition, blocking medications usually provide transient effects and require frequent administration, which further increases the chance to compromise immunity. In this regard, myelin-specific therapy may provide the desired specificity and a long-lasting therapeutic effect by inducing myelin-specific regulatory T (T
reg) cells. Tolerogenic dendritic cells (TolDCs) are one such therapy. However,
ex vivo generated TolDCs may be converted into immunogenic DCs in a proinflammatory environment. In this study, we identified a potential novel myelin-specific therapy that works with immunogenic DCs, hence without the
in vivo conversion concern. We showed that immunization with DCs, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase for
de novo synthesis of a focally high 1,25-dihydroxyvitamin D concentration in the peripheral lymphoid tissues, induced T
reg cells. In addition, such engineered DCs, when pulsed with a myelin antigen, led to myelin-specific suppression of ongoing experimental allergic encephalomyelitis (an MS animal model), and the disease suppression depended on forkhead-box-protein-P3(foxp3)
+ T
reg cells. Our data support a novel concept that immunogenic DCs can be engineered for myelin-specific therapy for MS.-Li, C.-H., Zhang, J., Baylink, D. J., Wang, X., Goparaju, N. B., Xu, Y., Wasnik, S., Cheng, Y., Berumen, E. C., Qin, X., Lau, K.-H. W., Tang, X. Dendritic cells, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase and pulsed with a myelin antigen, provide myelin-specific suppression of ongoing experimental allergic encephalomyelitis.
AB - Multiple sclerosis (MS) is caused by immune-mediated damage of myelin sheath. Current therapies aim to block such immune responses. However, this blocking is not sufficiently specific and hence compromises immunity, leading to severe side effects. In addition, blocking medications usually provide transient effects and require frequent administration, which further increases the chance to compromise immunity. In this regard, myelin-specific therapy may provide the desired specificity and a long-lasting therapeutic effect by inducing myelin-specific regulatory T (T
reg) cells. Tolerogenic dendritic cells (TolDCs) are one such therapy. However,
ex vivo generated TolDCs may be converted into immunogenic DCs in a proinflammatory environment. In this study, we identified a potential novel myelin-specific therapy that works with immunogenic DCs, hence without the
in vivo conversion concern. We showed that immunization with DCs, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase for
de novo synthesis of a focally high 1,25-dihydroxyvitamin D concentration in the peripheral lymphoid tissues, induced T
reg cells. In addition, such engineered DCs, when pulsed with a myelin antigen, led to myelin-specific suppression of ongoing experimental allergic encephalomyelitis (an MS animal model), and the disease suppression depended on forkhead-box-protein-P3(foxp3)
+ T
reg cells. Our data support a novel concept that immunogenic DCs can be engineered for myelin-specific therapy for MS.-Li, C.-H., Zhang, J., Baylink, D. J., Wang, X., Goparaju, N. B., Xu, Y., Wasnik, S., Cheng, Y., Berumen, E. C., Qin, X., Lau, K.-H. W., Tang, X. Dendritic cells, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase and pulsed with a myelin antigen, provide myelin-specific suppression of ongoing experimental allergic encephalomyelitis.
KW - 1,25(OH)2D, foxp3
KW - Multiple sclerosis
KW - Regulatory T cells
KW - Treg
KW - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics
KW - Antigens
KW - Cell Line
KW - Mice, Inbred C57BL
KW - Cells, Cultured
KW - Dendritic Cells/metabolism
KW - Forkhead Transcription Factors/genetics
KW - Lymphoid Tissue
KW - T-Lymphocytes, Regulatory/metabolism
KW - Animals
KW - Bone Marrow Cells
KW - Encephalomyelitis, Autoimmune, Experimental/therapy
KW - Myelin Sheath
KW - Female
KW - Mice
KW - Gene Expression Regulation, Enzymologic/immunology
UR - http://www.scopus.com/inward/record.url?scp=85021660156&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021660156&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/431f0d04-574e-3493-89ff-66219e4c520d/
U2 - 10.1096/fj.201601243R
DO - 10.1096/fj.201601243R
M3 - Meeting abstract
C2 - 28363955
SN - 0892-6638
VL - 31
SP - 2996
EP - 3006
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -