T Helper Type 17 Immune Response Plays an Indispensable Role for Development of Iodine-Induced Autoimmune Thyroiditis in Nonobese Diabetic-H2h4 Mice

Abstract

T helper type 1(Th1)/Th2 paradigm has been expanded by discovery of a novel effector T cell (T(eff)) subset, Th17 cells, which produce a proinflammatory cytokine IL-17. Th17 cells have recently been shown to play a major role in numerous autoimmune diseases that had previously been thought to be Th1-dominant diseases. We here studied the significance of Th17 cells in iodine-induced autoimmune thyroiditis in nonobese diabetic-H2(h4) mice, a mouse model of Hashimoto's thyroiditis in humans, which spontaneously develop antithyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in the drinking water. We observed increased numbers of Th1 and Th17 cells in spleen and accumulation of both types of T(eff) in the thyroid glands of iodine-fed wild-type mice, indicating that Th17 cells as well as Th1 cells constitute thyroid lesions. Furthermore, the incidence and severity of intrathyroidal lymphocyte infiltration, and the titers of antithyroglobulin autoantibodies were markedly reduced in iodine-treated IL-17(-/-) mice as compared with wild-type mice. Of interest, IL-17(+/-) mice showed an intermediate phenotype. Therefore, the present study, together with a previous report demonstrating the importance of Th1, not Th2, immune response for developing thyroiditis using mice deficient for interferon-gamma or IL-4, clearly indicates that both Th1 and Th17 cells are critical T(eff) subsets for the pathogenesis of spontaneous autoimmune thyroiditis in nonobese diabetic-H2(h4) mice.

Serum interleukin-23 (IL-23) is increased in Hashimoto’s thyroiditis

“…reported in their study on 13 HT patients, reachs statistical relevance in our study, due to the high number of subjects studied. These data suggest that IL-23 is involved in the development of HT and further support the role of Th17 cells in AITD, in line with the data from the literature [7][8][9]21]. An enhanced production of IL-23 by APCs may drive the immune response towards a Th17 phenotype and contribute to promote the autoimmune inflammation of the gland.…”

“…A real-time 2D apparatus (General Electric IL-17, IL-21 and IL-22, is involved in numerous autoimmune diseases (AID) commonly thought to be Th1 diseases, including HT [6][7][8][9]. Moreover, the proportion of peripheral Th17 cells has been found to be higher in patients affected by severe GD than in GD patients in remission [9].…”

25-Hydroxyvitamin D serum level in Hashimoto’s thyroiditis, but not Graves’ disease is relatively deficient

“…Wang et al found direct injection of TNF-α into the thyroids of mTg-primed mice can induce thyrocyte apoptosis, indicating that pro-inflammatory TNF-α may play a critical role in thyroid destruction [14]. Horie I et al disclosed Th17 cells are critical for the pathogenesis of spontaneous autoimmune thyroiditis while Th17 cells were also shown to induce GD in NOD-H2(h4), but not in BALB/c mice, thus showing that the effect of IL-17 may also differ with the genetic background [15,16].…”

Increased differentiation of Th22 cells in Hashimoto^|^rsquo;s thyroiditis

“…Previous studies have shown that Th17 cells have a key, independent role in thyroiditis in NOD.H-2 h4 mice [14]. To the best of our knowledge, this is the first report of Th22 cells in NOD.H-2 h4 mice.…”