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Publication : Lymphotoxin pathway-directed, autoimmune regulator-independent central tolerance to arthritogenic collagen.

First Author  Chin RK Year  2006
Journal  J Immunol Volume  177
Issue  1 Pages  290-7
PubMed ID  16785524 Mgi Jnum  J:134431
Mgi Id  MGI:3785682 Doi  10.4049/jimmunol.177.1.290
Citation  Chin RK, et al. (2006) Lymphotoxin pathway-directed, autoimmune regulator-independent central tolerance to arthritogenic collagen. J Immunol 177(1):290-7
abstractText  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.
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