Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Clinical Reviews in Allergy and Immunology Année : 2017

Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus.

Résumé

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 and production of specific autoantibodies) and -independent (polyclonal B cell activation, production of autoantibodies by long-lived plasma cells). By providing a comprehensive evaluation of B and T cell surface markers in two major mouse models of SLE and a description of their changes before and after disease onset, this review illustrates how the study of lymphoid cell phenotype delivers key information regarding pathogenic pathways and supplies tools to assess the beneficial effects of novel therapeutic interventions.

Domaines

Immunologie
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Dates et versions

hal-01528593 , version 1 (29-05-2017)

Identifiants

Citer

Aurélie de Groof, Patrice Hémon, Olivier Mignen, Jacques-Olivier Pers, Edward K Wakeland, et al.. Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus.. Clinical Reviews in Allergy and Immunology, 2017, ⟨10.1007/s12016-017-8605-8⟩. ⟨hal-01528593⟩
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