Moreover, the enhanced expression of in RA monocytes reduces both the apoptosis by targeting caspase 10 (CASP10), apoptotic peptidase activating factor 1 (APAF1), and the expression of the chemokine C-C motif chemokine receptor 2 (CCR2), whereas increases the C-C motif chemokine receptor 7 (CCR7) and the secretion of C-C motif chemokine receptor 3/4/5 and 8 (CCL3, CCL4, CCL5, and CCL8). with HMs. Here we report the most recent discoveries on the miRNAs-based molecular mechanisms in those diseases that show clinical associations between the loss of immune tolerance and blood Sulfosuccinimidyl oleate cancer [22,23]. 2. MiRNAs in Autoimmune Diseases Autoimmunity originates from the breakdown of self-tolerance. This leads to the imbalance between the activation of the lymphocytes and the mechanisms responsible for their control. The most common mechanisms associated with the autoimmunity include: (i) innate immune cell hyperactivation, such as dendritic and macrophage cells if functionally defective, can overstimulate T lymphocytes; (ii) lack of apoptosis of self-reactive B or T helper (Th) cells; (iii) curtailed presence of regulatory T cells; (iv) inflammation. MicroRNAs have been reported to have a role in each of these mechanisms. 2.1. Involvement of microRNAs in Innate Immune Cells Hyperactivation and Inflammation Activate phenotype of the innate immune cells can over stimulate autoreactive T lymphocytes and produces pro-inflammatory cytokines. However, inflammation in autoimmune disease occurs also through the production of cytokines from other tissue-specific cells implicated in the pathology. Finally, chronic inflammation may result in fibrosis, which is common in certain ADs. Several miRNAs interfere with specific pathways related to the hyperactivation of the innate immune cells or pro-inflammatory cytokines and fibrotic tissue productions. acts into macrophages and dendritic cells from patients with ADs by altering their functions. It is overexpressed in macrophages resident in the membrane-lining layer and in CD14+ cells from synovial fluid of patients with rheumatoid arthritis (RA). Moreover, the enhanced expression of in RA monocytes reduces both the apoptosis by targeting caspase 10 (CASP10), apoptotic peptidase activating factor 1 (APAF1), and the expression of the chemokine C-C motif chemokine receptor 2 (CCR2), whereas increases the C-C motif chemokine receptor 7 (CCR7) and the secretion of C-C motif chemokine receptor 3/4/5 and 8 (CCL3, CCL4, CCL5, and CCL8). In CD14 from peripheral blood, it leads to the production of pro-inflammatory cytokines tumor necrosis factor and interleukin 6 (TNF, also known as TNF and IL-6) as well as to the reduction of its direct target inositol polyphosphate-5-phosphatase D (INPP5D, also known as SHIP1), which is an inhibitor of inflammation. All these events favor the recruitment of leukocytes and the inflammation in RA [24,25,26]. SHIP1 is a target of also in dendritic cells (DCs). It was demonstrated that in a specific murine model the transfer of DCs pulsed with a self-antigen and matured following Toll-like-receptor (TLR) activation can induce autoimmunity. DCs over-expressing can break the immune tolerance also in the absence of TLR stimuli . However, is part of the TLR signalling. Its manifestation raises by Toll-like receptor 7 (TLR7) stimuli in plasmacytoid DCs from New Zealand Sulfosuccinimidyl oleate Black/White colored F1 cross (NZB/W F1) mice with symptomatic lupus, leading to the manifestation of the CD40 co-stimulatory molecule required to facilitate the T cell activation . can be considered mainly because an effector of the inflammasome signaling in SSc. Its high manifestation reported in SSc lung fibroblasts is definitely mediated by NLR family pyrin domain comprising 3 (NLRP3) inflammasome PRKD3 and is required for the synthesis of collagen, whose build up induces fibrosis . Additional miRNAs such as were found to interfere with the type I IFN signaling. Plasmacytoid DCs from individuals with SLE produce INF upon TLR7 ligand activation through exosomes-delivered micRNAs (and are downregulated in kidney cells from lupus nephritis or in monocytes from SLE and have like a target the interferon regulatory element 1 and 9 respectively (IRF1; IRF9), which are involved in type I IFN response [31,32]. The manifestation of is instead upregulated in SSc by transforming growth element beta (TGF-) signaling. With this context, it focuses on the peroxisome proliferator-activated receptor gamma (PPAR), an antagonist of the pro-fibrotic TGF- signaling and increases the level of fibrotic-related genes . In SSc, promotes the secretion of IFNA1 in plasmocytoid Sulfosuccinimidyl oleate DCs in SSc . In monocytes Sulfosuccinimidyl oleate from SLE individuals, the type I IFN inhibits the maturation of contributing to uncontrolled swelling [35,36]. In mice,.