Expression of class II major histocompatibility complex molecules on thyrocytes does not cause spontaneous thyroiditis but mildly increases its severity after immunization

Hiroaki Kimura, Miho Kimura, Shey-Cherng Tzou, Yen Chun Chen, Koichi Suzuki, Noel R. Rose, Patrizio Caturegli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Class II major histocompatibility complex (MHC) molecules are classically expressed on antigen-presenting cells of the hematopoietic lineage but have also been described on epithelial cells in association with autoimmunity. In this context, however, it remains debatable whether class II MHC molecules are the initiating event or rather the consequence of the autoimmune attack. In addition, the role of epithelial class II expression once the autoimmune attack has begun is unknown. We generated transgenic mice expressing in the thyroid follicular cells the class II transactivator, the master regulator of all the genes in the class II MHC pathway. The study used a cohort of 245 CBA/J mice (127 wild-type and 118 transgenic), both in basal conditions (n = 63) and at different time points after immunization with mouse thyroglobulin (n = 182). In basal conditions, transgenic mice were similar to wild-type controls and did not develop spontaneous autoimmune thyroiditis, despite the aberrant expression of class II MHC molecules on thyrocytes. After immunization, thyroiditis was 8% more severe in transgenics than controls (85% confidence interval from 1.8-13.4%; P = 0.033), especially during the florid stages of disease. These findings suggest that expression of class II MHC molecules on epithelial cells is not sufficient to initiate autoimmunity but mildly modulates an already established autoimmune attack against the target organ.

Original languageEnglish
Pages (from-to)1154-1162
Number of pages9
JournalEndocrinology
Volume146
Issue number3
DOIs
StatePublished - 1 Mar 2005

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