Lymphotoxm pathway-directed, autoimmune regulator-independent central tolerance to arthritogenic collagen

Robert K. Chin, Mingzhao Zhu, Peter A. Christiansen, Wenhua Liu, Carl Ware, Leena Peltonen, Xuejun Zhang, Linjie Guo, Shuhua Han, Biao Zheng, Yang Xin Fu

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Abstract

Ectopic expression of peripherally restricted Ags by medullary thymic epithelial cells (mTECs) is associated with negative selection. Autoimmune regulator (AIRE) is considered to be the master regulator of these Ags. We show in this study that the ectopic expression of type II collagen (CII) in mTECs and the corresponding central tolerance to CII are AIRE independent but lymphotoxin dependent. The failure to properly express CII in mTECs of Lta-/- and Ltbr-/- mice leads to overt autoimmunity to CII and exquisite susceptibility to arthritis. These findings define the existence of additional pathways of ectopic peripheral Ag expression, parallel to and independent of AIRE, which may cover an extended spectrum of peripheral Ags in the thymus.

Original languageEnglish (US)
Pages (from-to)290-297
Number of pages8
JournalJournal of Immunology
Volume177
Issue number1
StatePublished - Jul 1 2006

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ASJC Scopus subject areas

  • Immunology

Cite this

Chin, R. K., Zhu, M., Christiansen, P. A., Liu, W., Ware, C., Peltonen, L., Zhang, X., Guo, L., Han, S., Zheng, B., & Fu, Y. X. (2006). Lymphotoxm pathway-directed, autoimmune regulator-independent central tolerance to arthritogenic collagen. Journal of Immunology, 177(1), 290-297.