Defective expression of regulatory B cells in iodine-induced autoimmune thyroiditis in non-obese diabetic H-2(h4) mice.
BACKGROUND
The ability of B cells to negatively regulate cellular immune responses and inflammation has been described. The regulatory B (Breg) cells with the unique CD1d(hi)CD5(+)CD19(+) phenotype and the capacity to produce IL-10 are potent negative regulators of inflammation and autoimmunity in several in vivo mouse models of autoimmune disease.


OBJECTIVE
To investigate whether Breg cell deficiency participates in autoimmune thyroiditis (AIT) in an animal model.


METHODS
Non-obese diabetic (NOD).H-2(h4) mice at 4 weeks of age were randomly divided into control and iodine-treated groups; the iodine-treated group received sterile water containing 0.005 % NaI for 10 or 20 weeks. The percentage of CD1d(hi)CD5(+)CD19(+) Bregs, CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg) and CD4(+)IL17(+) T helper 17 cells (Th17) in splenic mononuclear cells was detected by multicolor flow cytometry. The expression of IL-10 mRNA and TGF-β mRNA in splenocytes was measured by real-time RT-PCR.


RESULTS
NOD.H-2(h4) mice spontaneously develop anti-thyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in drinking water. Mice with AIT had a decreased CD1d(hi)CD5(+)CD19(+) Breg subset and reduced IL-10 mRNA expression in splenocytes compared with controls (p < 0.05) and maintained relatively low levels during the development of thyroiditis. The proportion of Breg cells was negatively correlated with the proportion of Th17 cells, but positively correlated with CD4(+)CD25(+)FoxP3(+) Treg cells in splenocytes (All p < 0.05).


CONCLUSIONS
The defective expression of Breg cells combined with impaired Treg cells and enhanced Th17 cells might play an important role in the development of iodine-induced AIT in NOD.H-2(h4) mice.
Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
L
L
Shi
M
M
Bi
R
R
Yang
J
J
Zhou
S
S
Zhao
C
C
Fan
Z
Z
Shan
Y
Y
Li
W
W
Teng
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D060151:B-Lymphocytes, Regulatory / Q000166:cytology*; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D012974:Sodium Iodide; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D001323:Autoantibodies; D016212:Transforming Growth Factor beta; C006606:anti-thyroglobulin; D016753:Interleukin-10; D012974:Sodium Iodide