Three checkpoints in lupus development: Central tolerance in adaptive immunity, peripheral amplification by innate immunity and end-organ inflammation

H. Kanta, C. Mohan

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Although the etiology of systemic lupus erythematosus (SLE) remains to be fully elucidated, it is now apparent that multiple genetic and environmental factors are at play. Over the past decade, several studies have helped uncover genetic associations and susceptibility loci in human and murine lupus. In particular, recent genome-wide association studies have uncovered a large number of associated genes in human SLE. Given this plethora of candidate genes, the next challenge for lupus biologists is to fathom how these different genes operate to engender lupus. In this context, recent genetic studies in mouse models of lupus have been particularly informative. The purpose of this review is to overview three key genetically determined checkpoints in lupus development that have emerged from studies of NZM2410-derived congenic strains bearing individual lupus susceptibility loci. These three events include a breach in central tolerance in the adaptive arm of the immune system, peripheral amplification of the autoimmune response by the innate immune system and local processes in the target organ that facilitate end-organ disease. Collectively, murine congenic dissection studies provide a framework for understanding and analyzing the steady stream of gene candidates that are currently emerging from human lupus studies.

Original languageEnglish (US)
Pages (from-to)390-396
Number of pages7
JournalGenes and Immunity
Volume10
Issue number5
DOIs
StatePublished - 2009

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Central Tolerance
Adaptive Immunity
Innate Immunity
Inflammation
Systemic Lupus Erythematosus
Genes
Immune System Phenomena
Genome-Wide Association Study
Genetic Predisposition to Disease
Autoimmunity
Dissection
Immune System

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Three checkpoints in lupus development : Central tolerance in adaptive immunity, peripheral amplification by innate immunity and end-organ inflammation. / Kanta, H.; Mohan, C.

In: Genes and Immunity, Vol. 10, No. 5, 2009, p. 390-396.

Research output: Contribution to journalArticle

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