Ana Cecilia Avalos - Academia.edu (original) (raw)
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Papers by Ana Cecilia Avalos
Autoimmunity, 2009
Immune complexes (ICs) containing DNA and RNA are responsible for disease manisfestations found i... more Immune complexes (ICs) containing DNA and RNA are responsible for disease manisfestations found in patients with Systemic Lupus Erythematosus (SLE). B cells contribute to SLE pathology through BCR recognition of endogenous DNA-and RNA-associated autoantigens and delivery of these self-constitutents to endosomal TLR9 and TLR7, respectively. B cell activation by these pathways leads to production of class-switched DNA-and RNA reactive autoantibodies, contributing to an inflammatory amplification loop characteristic of disease. Intriguinly, self-DNA and RNA are typically non-stimulatory for TLR9/7 due to absence of stimulatory sequences or presence of molecular modifications. Recent evidence from our lab and others suggests that B cell activation by BCR/TLR pathways is tightly regulated by surface-expressed receptors on B cells, and the outcome of activation depends on the balance of stimulatory and inhibitory signals. Either IFNα engagement of the type I IFN receptor, or loss of IgG ligation of the inhibitory FcγRIIB receptor promotes B cell activation by weakly-stimulatory DNA and RNA TLR ligands. In this context, autoreactive B cells can respond robustly to common autoantigens. These findings have important implications for the role of B cells in vivo in the pathology of SLE.
Autoimmunity, 2009
Immune complexes (ICs) containing DNA and RNA are responsible for disease manisfestations found i... more Immune complexes (ICs) containing DNA and RNA are responsible for disease manisfestations found in patients with Systemic Lupus Erythematosus (SLE). B cells contribute to SLE pathology through BCR recognition of endogenous DNA-and RNA-associated autoantigens and delivery of these self-constitutents to endosomal TLR9 and TLR7, respectively. B cell activation by these pathways leads to production of class-switched DNA-and RNA reactive autoantibodies, contributing to an inflammatory amplification loop characteristic of disease. Intriguinly, self-DNA and RNA are typically non-stimulatory for TLR9/7 due to absence of stimulatory sequences or presence of molecular modifications. Recent evidence from our lab and others suggests that B cell activation by BCR/TLR pathways is tightly regulated by surface-expressed receptors on B cells, and the outcome of activation depends on the balance of stimulatory and inhibitory signals. Either IFNα engagement of the type I IFN receptor, or loss of IgG ligation of the inhibitory FcγRIIB receptor promotes B cell activation by weakly-stimulatory DNA and RNA TLR ligands. In this context, autoreactive B cells can respond robustly to common autoantigens. These findings have important implications for the role of B cells in vivo in the pathology of SLE.