Undenatured type II collagen protects against collagen-induced arthritis by restoring gut-joint homeostasis and immunity

Oral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear. We used undenatured type II collagen in a prophylactic regime -7.33 mg/kg three times/week- to describe the mechanisms associated with protective oral immune-therapy (OIT) in gut and joint during experimental Collagen-Induced Arthritis (CIA). OIT reduced disease incidence to 50%, with reduced expression of IL-17 and IL-22 in the joints of asymptomatic mice. Moreover, whilst the gut tissue of arthritic mice shows substantial damage and activation of tissue-specific immune networks, oral administration of undenatured type II collagen protects against gut pathology in all mice, symptomatic and asymptomatic, rewiring IL-17/IL-22 networks. Furthermore, gut fucosylation and microbiome composition were also modulated. These results corroborate the relevance of the gut-joint axis in arthritis, showing novel regulatory mechanisms linked to therapeutic OIT in joint disease

The parasitic worm product ES- 62 protects against collageninduced arthritis by resetting the gut-bone marrow axis in a microbiome-dependent manner

The parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62’s prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA mice. As the status of the gut microbiota impacts on immune responses by influencing haematopoiesis, we have therefore investigated whether ES-62 harnesses the homeostatic mechanisms regulating this gut-bone marrow (BM) axis to resolve the chronic inflammation promoting autoimmunity and joint destruction in CIA. Reflecting this, ES-62 was found to counteract the BM myeloid/lymphoid bias typically associated with chronic inflammation and infection. This was achieved primarily by ES-62 acting to maintain the levels of lymphoid lineages (B220+ and CD3+ cells) observed in naïve, healthy mice but lost from the BM of CIA-mice. Moreover, ES-62’s ability to prevent bone-destroying osteoclastogenesis was found to be associated with its suppression of CIA-induced upregulation of osteoclast progenitors (OCPs) in the BM. Critically, and supporting ES-62’s targeting of the gut-BM axis, this rewiring of inflammatory haematopoiesis was lost in mice with a depleted microbiome. Underlining the importance of ES-62’s actions in restoring steady-state haematopoiesis, the BM levels of B and T lymphoid cells were shown to be inversely correlated, whilst the levels of OCPs positively correlated, with the severity of joint damage in CIA-mice

The role of gut tissue in arthritis: unravelling glycomic and inflammatory networks underlying immunoregulation

Abstract not currently available

Synovial fibroblast sialylation regulates cell migration and activation of inflammatory pathways in arthritogenesis

Synovial fibroblasts have emerged as critical underlying factors to perpetuate chronic joint inflammation in Rheumatoid Arthritis. Like any other cell, synovial fibroblasts are covered with a complex layer of glycans that can change in response to extracellular signals, such as inflammation. We have previously shown that inflammatory synovial fibroblasts show decreased levels of sialic acid, but our understanding of sialic acid-dependent pathophysiological pathways in these stromal cells is still very limited. In this report, we used in vivo and in vitro studies with exogenous sialidases and RNA sequencing to investigate the responses of murine synovial fibroblasts upon desialylation. Our results show that hyposialylated fibroblasts present a dysregulated migratory ability and an activated phenotype characterized by the expression of inflammatory mediators, such as cytokines and chemokines, and anti-viral related mechanisms. Removal of surface sialic acid also affected the expression of sialyltransferases, revealing the existence of a positive feedback to sustain reduced sialylation. Moreover, we demonstrate that synovial fibroblasts subsets have distinct sialyltransferase expression profiles, both in healthy and arthritic mice. These findings underline the ability of sialic acid to modulate homeostatic and inflammatory responses in non-immune synovial fibroblasts, suggesting that sialylation plays a key role in perpetuating local inflammation in the arthritic joint

A Comprehensive Analysis of Clinical Crowns in Young of Han Nationality with Normal Occlusion Using Intraoral Scanning

Background. The measurement and analysis of clinical crowns play a crucial role in stomatology, anthropology, and studies of genetic and environmental variables in oral and maxillofacial development. Purpose. The objective of the present study was to measure the parameters of clinical crowns of permanent dentition in youth of Han nationality using intraoral scanning and identify potential influencing factors. Materials and Methods. A total of 100 subjects (50 males and 50 females) of Han nationality aged 18–24 with normal occlusion were selected. An intraoral scanner was used to obtain the digital dental impressions, and Materialise Magics 21 software was used to measure the mesiodistal diameter (MDD), buccolingual diameter (BLD), height, mesiodistal angle (MDA), and vestibulo-oral angle (VOA) of clinical crowns. The central height was calculated based on the height of clinical crowns. SPSS 27.0 software was used for statistical analysis. The two-independent-samplet-test was used to assess discrepancies in clinical crowns between males and females. The paired t-test was used to determine differences between antimetric pairs of clinical crowns within the same arch. The repeatability of intraoral scanning was tested using the paired t-test between two measurements at one-month intervals. The overall estimated effect was considered significant where P < 0.05. Results. The MDD, BLD, height, MDA, and VOA of clinical crowns in the youth of Han nationality were measured, and the central height was calculated. No significant difference was found in terms of MDA and VOA between genders and antimetric pairs within the same arch. Regarding the distance parameters, the MDD, BLD, and height of clinical crowns in males were significantly larger than those in females (MDD: U1, U3, U7, L2, L3, L6, and L7: P<0.01; BLD: U1: P=0.02; U3–U7 and L1–L7: P<0.01; height: U2: P=0.03; and U1, U3–U7, and L3–L7: P<0.01). No significant difference was found in clinical crowns between antimetric pairs within the same arch. Intraoral scanning demonstrated good repeatability in the measurement of clinical crowns. Conclusions. Apart from MDA and VOA, the parameters of clinical crowns in males were significantly larger than in females. Antimetric pairs of clinical crowns within the same arch demonstrated similar tooth dimensions. In future clinical practice and scientific research in the oral and maxillofacial region, a comprehensive design of sexual and ethnic characteristics should be considered

The parasitic worm product ES-62 protects against collagen-induced arthritis by resetting the gut-bone marrow axis in a microbiome-dependent manner

The parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62’s prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA-mice. As the status of the gut microbiota impacts on immune responses by influencing haematopoiesis, we have therefore investigated whether ES-62 harnesses the homeostatic mechanisms regulating this gut-bone marrow (BM) axis to resolve the chronic inflammation promoting autoimmunity and joint destruction in CIA. Reflecting this, ES-62 was found to counteract the BM myeloid/lymphoid bias typically associated with chronic inflammation and infection. This was achieved primarily by ES-62 acting to maintain the levels of lymphoid lineages (B220+ and CD3+ cells) observed in naïve, healthy mice but lost from the BM of CIA-mice. Moreover, ES-62’s ability to prevent bone-destroying osteoclastogenesis was found to be associated with its suppression of CIA-induced upregulation of osteoclast progenitors (OCPs) in the BM. Critically, and supporting ES-62’s targeting of the gut-BM axis, this rewiring of inflammatory haematopoiesis was lost in mice with a depleted microbiome. Underlining the importance of ES-62’s actions in restoring steady-state haematopoiesis, the BM levels of B and T lymphoid cells were shown to be inversely correlated, whilst the levels of OCPs positively correlated, with the severity of joint damage in CIA-mice