CXCL10 DNA vaccination prevents spontaneous diabetes through enhanced beta cell proliferation in NOD mice.
CXCL10, a chemokine for Th1 cells, is involved in the pathogenesis of various Th1-dominant autoimmune diseases. Type 1 diabetes is considered to be a Th1-dominant autoimmune disease, and a suppressive effect of CXCL10 neutralization on diabetes development has been reported in a cyclophosphamide-induced accelerated diabetes model through induction of beta cell proliferation. However, intervention in a diabetes model might bring about opposite effects, depending on the timing, amount, or method of treatment. In the present study, we examined the effect of CXCL10 neutralization in a "spontaneous diabetes" model of NOD mice, using CXCL10 DNA vaccination (pCAGGS-CXCL10). pCAGGS-CXCL10 treatment in young NOD mice induced the production of anti-CXCL10 Ab in vivo and suppressed the incidence of spontaneous diabetes, although this treatment did not inhibit insulitis or alter the immunological response. pCAGGS-CXCL10 treatment enhanced the proliferation of pancreatic beta cells, resulting in an increase of beta cell mass in this spontaneous diabetes model as well. Therefore, CXCL10 neutralization is suggested to be useful for maintaining beta cell mass at any stage of autoimmune diabetes.
Shigihara
Toshikatsu
T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Shimada
Akira
A
Oikawa
Yoichi
Y
Yoneyama
Hiroyuki
H
Kanazawa
Yasuhiko
Y
Okubo
Yoshiaki
Y
Matsushima
Kouji
K
Yamato
Eiji
E
Miyazaki
Jun-Ichi
J
Kasuga
Akira
A
Saruta
Takao
T
Narumi
Shosaku
S
D000818:Animals; D000917:Antibody Formation; D049109:Cell Proliferation; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D050417:Insulin-Secreting Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D010957:Plasmids; D019444:Vaccines, DNA
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; D016207:Cytokines; D019444:Vaccines, DNA