S4 B). general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens. Graphical Abstract Open in a separate window Introduction A feature of autoimmune diseases is the secretion of specific autoantibodies by terminally differentiated B cells, plasma cells (PCs). IgA- and IgM-secreting PCs are abundant IWP-3 in the lamina propria in the gut, where antibodies are secreted and transported into the intestinal lumen. Traditionally, gut PCs were thought to be short-lived antibody factories, and other potential roles of PCs in health and autoimmune diseases have not been under much investigation. However, expression of HLA class II molecules and costimulatory molecules such as CD40, CD80, and CD86, as well as cytokine secretion, suggests that PCs can have additional functions (Ellyard et al., 2004; Fillatreau, 2015; Fritz et al., 2012; H?ydahl et al., 2019; Pelletier et al., 2010). Recently, based on cell-turnover analysis in gut transplants and by retrospective cell-birth dating measuring carbon-14 in genomic DNA, three subsets of short-, intermediate-, and long-lived IWP-3 lamina propria PCs with distinct expression of cell surface markers CD19 and CD45 were described (Landsverk et al., 2017). The longevity profile of human gut PCs in a disease setting is yet uncharacterized. Celiac disease (CeD) is associated with a highly specific autoantibody response. The patients have autoantibodies to the enzyme transglutaminase 2 (TG2) as well as antibodies to deamidated gluten peptides (DGPs; Iversen and Sollid, 2020). The disease is driven by an immune response to cereal gluten proteins, which explains the presence of the DGP antibodies. TG2 is involved in the pathogenesis by catalyzing deamidation of gluten peptides. The patients have CD4+ T cells that recognize DGP bound Col4a4 to disease-associated HLA-DQ molecules (Molberg et al., 1998). These T cells likely provide T cell help to DGP-specific B cells as well as TG2-specific B cells; the latter by involvement IWP-3 of TG2-gluten IWP-3 peptide hapten-carrierClike molecules (Iversen and Sollid, 2020). The disease lesion in the small intestine is characterized by blunting of villi and infiltration of inflammatory cells, including PCs. The active lesion typically has a two- to threefold increased density of IgA and IgM PCs in lamina propria (Baklien et al., 1977), with 10% of the Personal computers being specific for TG2 and 1% becoming specific for DGP (Di Niro et al., 2010; Steinsb? et al., 2014). The only available treatment for CeD is definitely adherence to a stringent gluten-free diet (GFD). After commencing a GFD, the concentration of disease-specific serum antibodies (Sugai et al., 2010) and quantity of disease-specific Personal computers in lamina propria drop within weeks (Di Niro et al., 2016). The part of Personal computers in CeD is currently unfamiliar, and it is uncertain to what extent the secreted autoantibodies perform a pathogenic part (Iversen et al., 2014; Lindfors et al., 2009). Recent reports have shown that intestinal Personal computers may have additional functions to antibody secretion, such as antigen demonstration and cytokine secretion (H?ydahl et al., 2019; Snir et al., 2019), leading to the hypothesis that disease-specific Personal computers are playing an active part in the pathogenesis of CeD, including having a role as APCs for gluten-specific T cells. Identifying functions of gut Personal computers could provide more knowledge about disease mechanisms and point out disease-specific Personal computers as therapeutic focuses on. IWP-3 High-throughput sequencing systems possess revolutionized the profiling of immune receptor repertoires in health and disease (AIRR-seq; Benichou et al., 2012; Yaari and Kleinstein, 2015), and we have previously applied these systems to dissect the repertoire of disease-specific Personal computers in CeD (Di Niro et al., 2012; Iversen et al., 2017; Roy et al., 2017; Snir et al., 2017; Snir et al., 2015; Steinsb? et al., 2014). However, little is known about the transcriptional state of these cells. The development of single-cell RNA-sequencing (scRNA-seq) protocols provides a unique tool to identify and characterize cell subsets relating to their.