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PMID: 18199416 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The lupus-related Lmb3 locus contains a disease-suppressing Coronin-1A gene mutation.

Immunity ·Vol. 28 ·No. 1 ·2008-01-00 ·Pages 40-51

Haraldsson MK, Louis-Dit-Sully CA, Lawson BR, Sternik G, Santiago-Raber ML, Gascoigne NR, Theofilopoulos AN, Kono DH

Abstract

Here, we show that a lupus-suppressing locus is caused by a nonsense mutation of the filamentous actin-inhibiting Coronin-1A gene. This mutation was associated with developmental and functional alterations in T cells including reduced migration, survival, activation, and Ca2+ flux. T-dependent humoral responses were impaired, but no intrinsic B cell defects were detected. By transfer of T cells, it was shown that suppression of autoimmunity could be accounted for by the presence of the Coro1a(Lmb3) mutation in T cells. Our results demonstrate that Coronin-1A is required for the development of systemic lupus and identify actin-cytoskeleton regulatory proteins as potential targets for modulating autoimmune diseases.

MeSH Terms
Actins/metabolism Adoptive Transfer Animals Apoptosis/physiology Autoantibodies/blood,immunology B-Lymphocytes/immunology Cell Proliferation Chemotaxis, Leukocyte/immunology Codon, Nonsense Enzyme-Linked Immunosorbent Assay Flow Cytometry Genetic Predisposition to Disease Immunoglobulin G/blood,immunology Immunohistochemistry Lupus Erythematosus, Systemic/genetics,immunology Lymphocyte Activation/immunology Mice Microfilament Proteins/genetics Polymerase Chain Reaction T-Lymphocytes/immunology Transfection
Chemicals
Actins Autoantibodies Codon, Nonsense Immunoglobulin G Microfilament Proteins coronin proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Haraldsson M Katarina
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Louis-Dit-Sully Christine A
Lawson Brian R
Sternik Gabriel
Santiago-Raber Marie-Laure
Gascoigne Nicholas R J
Theofilopoulos Argyrios N
Kono Dwight H
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1074-7613
DOI
10.1016/j.immuni.2007.11.023
Published
2008-01-00
Pages
40-51
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2274909
Subset
IM
Grants
NIAMS NIH HHS · R01 AR039555 · United States
NIAMS NIH HHS · AR42242 · United States
NIAMS NIH HHS · R01 AR031203-24 · United States
NIAMS NIH HHS · AR39555 · United States
NIAMS NIH HHS · R01 AR031203 · United States
NIAMS NIH HHS · R37 AR039555 · United States
NIAID NIH HHS · AI051977 · United States
NIGMS NIH HHS · R01 GM065230 · United States
NIGMS NIH HHS · GM65230 · United States
NIAMS NIH HHS · AR31203 · United States
NIAMS NIH HHS · R01 AR042242 · United States
NIAMS NIH HHS · R01 AR039555-13 · United States
Corrections
CommentIn
PMID: 18199411
External Links
PubMed source DOI: 10.1016/j.immuni.2007.11.023 PMC Full Text View journal details
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