Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus

Clinical Reviews in Allergy & Immunology
Aurélie De GroofBernard R Lauwerys

Abstract

Biases in the distribution and phenotype of T, B, and antigen-presenting cell populations are strongly connected to mechanisms of disease development in mouse models of systemic lupus erythematosus (SLE). Here, we describe longitudinal changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and spleen from two lupus-prone strains (MRL/lpr and B6.Sle1.Sle2.Sle3 tri-congenic mice), and how they integrate in our present understanding of the pathogenesis of the disease. In particular, we focus on (autoreactive) T cell activation patterns in lupus-prone mice. Break of T cell tolerance to chromatin constituents (histone peptides) is key to the development of the disease and is related to T cell intrinsic defects, contributed by genetic susceptibility factors and by extrinsic amplificatory mechanisms, in particular over-stimulation by antigen-presenting cells. We also describe shifts in B cell sub-populations, going from skewed immature B cell populations as an indication of disturbed central and peripheral tolerance checkpoints, to enriched long-lived plasma cells, which are key to persistent autoantibody production in the disease. B cell activation mechanisms in SLE are both T cell-dependent (break of tolerance...Continue Reading

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Citations

Jul 28, 2018·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Sep 27, 2019·Cells·Joshua GartonCarol F Webb
May 10, 2017·Clinical Reviews in Allergy & Immunology·Yves Renaudineau
Jan 24, 2019·Mediators of Inflammation·Wakako YamamotoMasahiro Hirayama
Apr 26, 2019·Cancer Immunology Research·Federica RivaCecilia Garlanda
Feb 13, 2021·Frontiers in Immunology·Sumie Hiramatsu-AsanoJun Wada

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