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From T to B and back again: positive feedback in systemic autoimmune disease

Abstract

Systemic lupus erythematosus, a prototypical systemic autoimmune disease, is the result of a series of interactions within the immune system that ultimately lead to the loss of self-tolerance to nuclear autoantigens. Here, we present an integrated model that explains how self-tolerance is initially lost and how the loss of tolerance is then amplified and maintained as a chronic autoimmune state. Key to this model are the self-reinforcing interactions of T and B cells, which we suggest lead to perpetuation of autoimmunity as well as its spread to multiple autoantigen targets.

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Figure 1: Mechanisms for the induction and amplification of lupus autoimmunity.
Figure 2: Mechanism of epitope spreading.

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Correspondence to Mark J. Shlomchik.

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DATABASES

LocusLink

B7RP1

TNF-β

MGI

B7h

BLyS

CD40

CD80

CD86

CD95

CD152

CD154

Icos

IL-2

PD-1

TNF

OMIM

systemic lupus erythematosus

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Shlomchik, M., Craft, J. & Mamula, M. From T to B and back again: positive feedback in systemic autoimmune disease. Nat Rev Immunol 1, 147–153 (2001). https://doi.org/10.1038/35100573

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