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Publication : Thyrocytes responding to IFN-gamma are essential for development of lymphocytic spontaneous autoimmune thyroiditis and inhibition of thyrocyte hyperplasia.

First Author  Yu S Year  2006
Journal  J Immunol Volume  176
Issue  2 Pages  1259-65
PubMed ID  16394017 Mgi Jnum  J:126438
Mgi Id  MGI:3761248 Doi  10.4049/jimmunol.176.2.1259
Citation  Yu S, et al. (2006) Thyrocytes responding to IFN-gamma are essential for development of lymphocytic spontaneous autoimmune thyroiditis and inhibition of thyrocyte hyperplasia. J Immunol 176(2):1259-65
abstractText  IFN-gamma promotes the development of lymphocytic spontaneous autoimmune thyroiditis (L-SAT) in NOD.H-2h4 mice and inhibits the development of thyrocyte hyperplasia and proliferation (TEC H/P). The precise mechanisms by which IFN-gamma promotes L-SAT and inhibits TEC H/P are unknown. To determine whether responsiveness of lymphocytes or thyrocytes to IFN-gamma is important for the development of these lesions, IFN-gammaR-/- mice, which develop TEC H/P similar to IFN-gamma-/- mice, were used as recipients for adoptive cell transfer. Wild-type (WT) splenocytes or bone marrow induced L-SAT and inhibited TEC H/P in IFN-gamma-/-, but not IFN-gammaR-/- recipients. IFN-gammaR-/- recipients of WT cells developed severe TEC H/P, but did not develop L-SAT, suggesting that thyrocytes responding to IFN-gamma are important for inhibition of TEC H/P. Unexpectedly, IFN-gammaR-/- splenocytes or bone marrow did not induce L-SAT in IFN-gamma-/- or WT mice even though IFN-gammaR-/- lymphocyte donors produced as much IFN-gamma as lymphocytes from WT donors, and thyrocytes could respond to IFN-gamma. Real-time PCR indicated that recipients of IFN-gammaR-/- bone marrow expressed less mRNA for IFN-gamma-inducible chemokines compared with recipients of WT bone marrow. This might limit the migration of IFN-gammaR-/- lymphocytes to thyroids. Few IFN-gammaR-/- lymphocytes infiltrated thyroids even in the presence of WT lymphocytes, suggesting that lymphocytes unable to respond to IFN-gamma are not induced to migrate to thyroids. These results suggest that thyrocytes must be able to respond to IFN-gamma for the development of L-SAT and inhibition of TEC H/P, and lymphocytes must be able to respond to IFN-gamma to induce L-SAT.
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