Prevention of lymphocytic thyroiditis in iodide-treated non-obese diabetic mice lacking interferon regulatory factor-1.
OBJECTIVE
Interferon regulatory factor-1 (IRF-1) is a critical regulator of interferon-gamma(IFNgamma)-mediated immune responses. To determine whether IRF-1 is involved in the pathogenesis of thyroiditis in animal models, we evaluated the incidence of iodide-induced lymphocytic thyroiditis (LT) in non-obese diabetic (NOD) mice lacking IRF-1 as well as IRF-1 +/+ and +/- mice.


METHODS
IRF-1 +/+, +/- and -/- NOD mice at 6 weeks of age were fed water (group 1) or iodide water (group 2) for 8 weeks.


METHODS
Thyroids were examined histopathologically and intrathyroidal lymphocytic infiltration was arbitrarily graded. Serum thyroxine (T(4)) and anti-mouse thyroglobulin antibody (anti-mTgAb) levels were measured. Spleen cell population was analyzed by flow cytometry, and IFNgamma and interleukin-10 produced by splenocytes were measured by enzyme-linked immunosorbent assay.


RESULTS
In group 1, only 4.3% of NOD mice developed LT. In contrast, 67.6% of mice in group 2 developed the disease. Iodide treatment induced LT in more than 80% of IRF-1 +/+ and +/- mice. However, no IRF-1 -/- mice in group 2 developed LT. There was no difference in both serum anti-mTgAb and T(4) levels among the three IRF-1 genotypes of NOD mice. Numbers of splenic CD8(+) T cells and IFNgamma production by Concanavalin A-stimulated splenocytes were markedly decreased in IRF-1-deficient NOD mice.


CONCLUSIONS
IRF-1 is involved in the development of iodide-induced LT in NOD mice.
Tani
Jun-ichi
J
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Mori
Kouki
K
Hoshikawa
Saeko
S
Nakazawa
Tetsuya
T
Satoh
Jo
J
Nakagawa
Yoshinori
Y
Ito
Sadayoshi
S
Yoshida
Katsumi
K
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism*; D015994:Incidence; D050856:Interferon Regulatory Factor-1; D007454:Iodides / Q000009:adverse effects* / Q000627:therapeutic use; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology*; D018345:Mice, Knockout / Q000235:genetics; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D007454:Iodides; C494258:Irf1 protein, mouse; D010750:Phosphoproteins