Genome and hormones: Gender differences in physiology selected contribution: Association of gender-related LMP2 inactivation with autoimmune pathogenesis

Citation
T. Hayashi et Dl. Faustman, Genome and hormones: Gender differences in physiology selected contribution: Association of gender-related LMP2 inactivation with autoimmune pathogenesis, J APP PHYSL, 91(6), 2001, pp. 2804-2815
Citations number
73
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
Journal title
JOURNAL OF APPLIED PHYSIOLOGY
ISSN journal
8750-7587 → ACNP
Volume
91
Issue
6
Year of publication
2001
Pages
2804 - 2815
Database
ISI
SICI code
8750-7587(200112)91:6<2804:GAHGDI>2.0.ZU;2-O
Abstract
Recent results in an animal model of autoimmune diabetes, the nonobese diab etic (NOD) mouse, suggest a hypothesis to explain the role of major histoco mpatibility complex (MHC) in autoimmunity. The genome MHC region contains i mmune response genes that are important for T cell education and antigen pr esentation by MHC molecules. Two such genes encoding the LMP2 and LMP7 prot easome subunits are located in this high-risk MHC genomic region. Proteasom e containing the LMP2 subunit is essential for T cell education and proteol ytically activates transcription factor nuclear factor-kappaB. Splenocytes of NOD mouse with marked female specificity for disease expression are defe ctive in LMP2 expression. The spontaneous defective LMP2 expression in NOD mice, which is gender biased toward female cohorts, is restricted to select lymphoid and myeloid cells and is developmentally controlled with lowered LMP2 protein and heightened tumor necrosis factor-alpha -induced apoptosis. These defects are apparent only after similar to7 wk of age. These data su ggest a proteasome role in autoimmune progression, and a gender development al and lineage restriction of LMP2 expression may contribute to the diverse autoimmune characteristics preferentially observed in female NOD mice.