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![Initiation of inflammatory arthritis. While infectious and gouty forms of IA are initiated by direct infection (1) or deposition of uric acid crystals (2) in joint‐associated tissues that triggers innate inflammatory processes, increasing evidence also supports a role for microbial interactions with the host in the initiation of autoimmune forms of arthritis [eg, rheumatoid arthritis (RA) and spondyloarthritis (SpA)]. For example, in preclinical RA, mucosal inflammatory processes and dysbiosis may drive the development of RA‐related anti‐citrullinated protein antibodies (ACPA) that are detectable at mucosal sites and/or in the circulation even in the absence of arthritic disease (3). This response may then spread to involve joint‐associated tissues (4). In addition, microbes and/or mechanical stress can drive IL‐23 production by entheseal myeloid cells to promote enthesitis (5), the major lesion in SpA patients, and accumulation of soluble urate reprograms myeloid cells toward a maladaptive inflammatory state that can promote arthritis (6). Moreover, inflammasome activation and subsequent production of IL‐1β/IL‐18 are key features in the development of many forms of IA (7). Collectively, these innate inflammatory processes may then promote dysregulation of adaptive immune responses that contribute to tissue damage in arthritic joints (8).](publication/339539836/figure/fig1/AS:11431281176069347@1690021098778/Initiation-of-inflammatory-arthritis-While-infectious-and-gouty-forms-of-IA-are.png)
Initiation of inflammatory arthritis. While infectious and gouty forms of IA are initiated by direct infection (1) or deposition of uric acid crystals (2) in joint‐associated tissues that triggers innate inflammatory processes, increasing evidence also supports a role for microbial interactions with the host in the initiation of autoimmune forms of arthritis [eg, rheumatoid arthritis (RA) and spondyloarthritis (SpA)]. For example, in preclinical RA, mucosal inflammatory processes and dysbiosis may drive the development of RA‐related anti‐citrullinated protein antibodies (ACPA) that are detectable at mucosal sites and/or in the circulation even in the absence of arthritic disease (3). This response may then spread to involve joint‐associated tissues (4). In addition, microbes and/or mechanical stress can drive IL‐23 production by entheseal myeloid cells to promote enthesitis (5), the major lesion in SpA patients, and accumulation of soluble urate reprograms myeloid cells toward a maladaptive inflammatory state that can promote arthritis (6). Moreover, inflammasome activation and subsequent production of IL‐1β/IL‐18 are key features in the development of many forms of IA (7). Collectively, these innate inflammatory processes may then promote dysregulation of adaptive immune responses that contribute to tissue damage in arthritic joints (8).
Citations
... The crosstalk between immune and skeletal systems, termed as "osteoimmunology," underlies bone physiological and pathological processes (Rho et al., 2004). The components of immune systems, such as immune cells and cytokines, are involved in bone remodeling and metabolic or inflammatory bone diseases, including osteoporosis, arthritis, and periodontitis (Weitzmann and Pacifi ci, 2006;Hajishengallis, 2015;Kuhn and Morrison, 2020). Periodontitis is an inflammation induced by exogenous pathogens. ...
Periodontitis is a polymicrobial infectious disease characterized by alveolar bone loss. Systemic diseases or local infections, such as diabetes, postmenopausal osteoporosis, obesity, and inflammatory bowel disease, promote the development and progression of periodontitis. Accumulating evidences have revealed the pivotal effects of gut microbiota on bone health via gut-alveolar-bone axis. Gut pathogens or metabolites may translocate to distant alveolar bone via circulation and regulate bone homeostasis. In addition, gut pathogens can induce aberrant gut immune responses and subsequent homing of immunocytes to distant organs, contributing to pathological bone loss. Gut microbial translocation also enhances systemic inflammation and induces trained myelopoiesis in the bone marrow, which potentially aggravates periodontitis. Furthermore, gut microbiota possibly affects bone health via regulating the production of hormone or hormone-like substances. In this review, we discussed the links between gut microbiota and periodontitis, with a particular focus on the underlying mechanisms of gut-bone axis by which systemic diseases or local infections contribute to the pathogenesis of periodontitis.
Rheumatoid arthritis (RA) is a systemic autoimmune disease with pathogenic inflammation caused partly by excessive cell‐free DNA (cfDNA). Specifically, cfDNA is internalized into immune cells, such as macrophages in lymphoid tissues and joints, and activates pattern recognition receptors, including cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS), resulting in overly strong proinflammation. Here, nanomedicine‐in‐hydrogel (NiH) is reported that co‐delivers cGAS inhibitor RU.521 (RU) and cfDNA‐scavenging cationic nanoparticles (cNPs) to draining lymph nodes (LNs) for systemic immunosuppression in RA therapy. Upon subcutaneous injection, NiH prolongs LN retention of RU and cNPs, which pharmacologically inhibit cGAS and scavenged cfDNA, respectively, to inhibit proinflammation. NiH elicits systemic immunosuppression, repolarizes macrophages, increases fractions of immunosuppressive cells, and decreases fractions of CD4⁺ T cells and T helper 17 cells. Such skewed immune milieu allows NiH to significantly inhibit RA progression in collagen‐induced arthritis mice. These studies underscore the great potential of NiH for RA immunotherapy.
