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Smitherman, C.

Publications and source records attributed to Smitherman, C..

2 recordsLinked to original sources
bioRxiv2023

An unconventional mechanism of IL-1β secretion that requires Type I IFN in lupus monocytes

Systemic Lupus Erythematosus (SLE) is characterized by autoreactive B cell activation, upregulation of Type I Interferon (IFN) and widespread inflammation. Mitochondrial nucleic acids (NAs) are increasingly recognized as triggers of IFN1. Thus, defective removal of mitochondria from mature red blood cells (Mito+ RBCs), a feature of SLE, contributes to IFN production by myeloid cells2. Here we identify blood monocytes (Mo) that have internalized RBCs and co-express IFN-stimulated genes (ISGs) and interleukin-1{beta} (IL-1{beta}) in SLE patients with active disease. We show that ISG expression requires the interaction between Mito+ RBC-derived mitochondrial DNA (mtDNA) and cGAS, while IL-1{beta} production entails Mito+ RBC-derived mitochondrial RNA (mtRNA) triggering of RIG-I-like receptors (RLRs). This leads to the cytosolic release of Mo-derived mtDNA that activates the NLRP3 inflammasome. Importantly, IL-1{beta} release depends on the IFN-inducible myxovirus resistant protein 1 (MxA), which enables the translocation of this cytokine into a trans-Golgi network (TGN)-mediated unconventional secretory pathway. Our study highlights a novel and synergistic pathway involving IFN and the NLRP3 inflammasome in SLE.

immunology↗
bioRxiv2019

Long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the niche cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells (LCs) led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active role in maintaining tissue homeostasis, which should be taken in consideration at data interpretation.

immunology↗