Faculty Collaboration Database

Deficiency in beta(2)-microglobulin, but not CD1, accelerates spontaneous lupus skin disease while inhibiting nephritis in MRL-Fas(lpr) nice: an example of disease regulation at the organ level. J Immunol 2001 Sep 01;167(5):2985-90

Date

08/18/2001

Pubmed ID

11509649

DOI

10.4049/jimmunol.167.5.2985

Scopus ID

2-s2.0-0035451795 (requires institutional sign-in at Scopus site)   71 Citations

Abstract

When mutations that inactivate molecules that function in the immune system have been crossed to murine lupus strains, the result has generally been a uniform up-regulation or down-regulation of autoimmune disease in the end organs. In the current work we report an interesting dissociation of target organ disease in beta(2)-microglobulin (beta(2)m)-deficient MRL-Fas(lpr) (MRL/lpr) mice: lupus skin lesions are accelerated, whereas nephritis is ameliorated. beta(2)m deficiency affects the expression of classical and nonclassical MHC molecules and thus prevents the normal development of CD8- as well as CD1-dependent NK1(+) T cells. To further define the mechanism by which beta(2)m deficiency accelerates skin disease, we studied CD1-deficient MRL/lpr mice. These mice do not have accelerated skin disease, excluding a CD1 or NK1(+) T cell-dependent mechanism of beta(2)m deficiency. The data indicate that the regulation of systemic disease is not solely governed by regulation of initial activation of autoreactive lymphocytes in secondary lymphoid tissue, as this is equally relevant to renal and skin diseases. Rather, regulation of autoimmunity can also occur at the target organ level, explaining the divergence of disease in skin and kidney in beta(2)m-deficient mice.

Author List

Chan OT, Paliwal V, McNiff JM, Park SH, Bendelac A, Shlomchik MJ

Author

Vipin Paliwal PhD Associate Professor in the Physics & Chemistry department at Milwaukee School of Engineering

MESH terms used to index this publication - Major topics in bold

Animals
Antigens, CD1
Female
Lupus Erythematosus, Cutaneous
Lupus Nephritis
Male
Mice
Mice, Inbred MRL lpr
Mice, Knockout
Organ Specificity
T-Lymphocyte Subsets
beta 2-Microglobulin