Macroautophagy is deregulated in murine and human lupus T lymphocytes

TLDR: Results suggest that autophagy could regulate the survival of autoreactive T cell during l upus, and could thus lead to design new therapeutic options for lupus.

Abstract: Macroautophagy was recently shown to regulate both lymphocyte biology and innate immunity In this study we sought to determine whether a deregulation of autophagy was linked to the development of autoimmunity Genome-wide association studies have pointed out nucleotide polymorphisms that can be associated with systemic lupus erythematosus, but the potential role of autophagy in the initiation and/or development of this syndrome is still unknown Here, we provide first clues of macroautophagy deregulation in lupus By the use of LC3 conversion assays and electron microscopy experiments, we observed that T cells from two distinct lupus-prone mouse models, ie, MRLlpr/lpr and (NZB/NZW)F1, exhibit high loads of autophagic compartments compared with nonpathologic control CBA/J and BALB/c mice Unlike normal mice, autophagy increases with age in murine lupus In vivo lipopolysaccharide stimulation in CBA/J control mice efficiently activates T lymphocytes but fails to upregulate formation of autophagic compartments in these cells This argues against a deregulation of autophagy in lupus T cells solely resulting from an acute inflammation injury Autophagic vacuoles quantified by electron microscopy are also found to be significantly more frequent in T cells from lupus patients compared with healthy controls and patients with non-lupus autoimmune diseases This elevated number of autophagic structures is not distributed homogeneously and appears to be more pronounced in certain T cells These results suggest that autophagy could regulate the survival of autoreactive T cell during lupus, and could thus lead to design new therapeutic options for lupus