Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Li, Xiaoya; Lü, Cheng; Fan, Danping; Lu, Xiangchen; Xia, Yu; Zhao, Hongyan; Xu, Huihui; Zhu, Yongliang; Li, Jingtao; Liu, Honglin; Xiao, Cheng

doi:10.3389/fcell.2020.00131

Cited by 40 publications

(31 citation statements)

References 43 publications

(60 reference statements)

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“…In a very recent study, human umbilical mesenchymal stem cells were transplanted in rats with CIA. Results showed that HUMSC transplantation reduced the pathology scores and the degree of bone damage in the ankles, favored the induction of Treg versus Th17 cells, increased the genera Bacteroides and Bacillus , and consistently upregulated ILA levels in plasma and AhR activation in the ileum [ 146 ]. The production of Trp metabolites, both in quality and quantity, is not the same among distinct bacteria strains.…”

Section: Amino Acid Metabolism By Microbiota and Ramentioning

confidence: 99%

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

et al. 2020

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In mammals, amino acid metabolism has evolved to act as a critical regulator of innate and adaptive immune responses. Rheumatoid arthritis (RA) is the most common form of inflammatory arthropathy sustained by autoimmune responses. We examine here the current knowledge of tryptophan and arginine metabolisms and the main immunoregulatory pathways in amino acid catabolism, in both RA patients and experimental models of arthritis. We found that l-tryptophan (Trp) metabolism and, in particular, the kynurenine pathway would exert protective effects in all experimental models and in some, but not all, RA patients, possibly due to single nucleotide polymorphisms in the gene coding for indoleamine 2,3-dioxygenase 1 (IDO1; the enzyme catalyzing the rate-limiting step of the kynurenine pathway). The function, i.e., either protective or pathogenetic, of the l-arginine (Arg) metabolism in RA was less clear. In fact, although immunoregulatory arginase 1 (ARG1) was highly induced at the synovial level in RA patients, its true functional role is still unknown, possibly because of few available preclinical data. Therefore, our analysis would indicate that amino acid metabolism represents a fruitful area of research for new drug targets for a more effective and safe therapy of RA and that further studies are demanding to pursue such an important objective.

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Section: Amino Acid Metabolism By Microbiota and Ramentioning

confidence: 99%

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

et al. 2020

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“…A previous study suggested that the functional heterogeneity of each GIT niche gives rise to regional-specific differences in the gut microbiota (Martinez-Guryn et al, 2019). Our previous study showed that the ileal microbial community of rats with CIA differed from that of the control group (Li et al, 2020). The ileum mainly functions to digest food, absorb nutrients, and develop intestinal mucosal immunity to protect against pathogens (Williams et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Regional Differences in the Gut Microbiota and Gut-Associated Immunologic Factors in the Ileum and Cecum of Rats With Collagen-Induced Arthritis

Cao

et al. 2020

Front. Pharmacol.

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Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation and a multifactorial etiology. We previously showed that gut microbiota dysbiosis in the rat ileum is involved in the development of collagen-induced arthritis (CIA). The gut microbiota in the distinct gastrointestinal tract (GIT) plays region-specific roles, but information on the different roles of the microbiota in distinct GIT compartments of CIA rats is limited. This study aimed to evaluate the region-specific differences in the gut microbial communities and certain gut-associated immunologic factors in the ileum and cecum of CIA rats. Ileal and cecal digesta were collected from CIA and control rats for microbiome analysis. We determined the microbial richness, diversity and taxa as well as the expression of interleukin (IL)-1β and IL-17A in the epithelium and lamina propria of the ileum and cecum mucosal layers. The CIA-induced microbiota alterations in the ileum differed from those in the cecum. The ileal microbiota were more markedly influenced in CIA, as revealed by sharp reductions in the abundances of the families Enterococcaceae, Lactobacillaceae and Streptococcaceae and the genera Lactobacillus and Lactococcus. Moreover, significant increases in IL-1β, and IL-17A mRNA expression were detected in only the ileal epithelium and lamina propria of the mucosal layer. Therefore, the microbial characteristics in the ileum were consistent with the immune-mediated inflammatory features of CIA, suggesting that the ileal microbiota might better represent the CIA-induced inflammatory responses than the cecal microbiota and that these responses might partially impact the progression of RA by regulating intestinal mucosal immunity.

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“…AhR can mediate crosstalk between ILCs and other immune cells in host tissues, especially in the intestinal mucosal surface [ 62 ], which may be the bridge between the gut microbiota and ICs. Li et al demonstrated that human umbilical mesenchymal stem cells played a therapeutic role in rats with CIA by modulating the interactions between the immune status of Treg, Th17 cells, and B cells and the gut microbiota in the ileum via AhR [ 63 ].…”

Section: Interactions Of the Gut Microbiota And Metabolites With Imentioning

confidence: 99%

Interactions between Gut Microbiota and Immunomodulatory Cells in Rheumatoid Arthritis

Zhao

Fan

et al. 2020

Mediators of Inflammation

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Rheumatoid arthritis (RA) is one of the most common autoimmune diseases caused by abnormal immune activation and immune tolerance. Immunomodulatory cells (ICs) play a critical role in the maintenance and homeostasis of normal immune function and in the pathogenesis of RA. The human gastrointestinal tract is inhabited by trillions of commensal microbiota on the mucosal surface that play a fundamental role in the induction, maintenance, and function of the host immune system. Gut microbiota dysbiosis can impact both the local and systemic immune systems and further contribute to various diseases, such as RA. The neighbouring intestinal ICs located in distinct intestinal mucosa may be the most likely intermediary by which the gut microbiota can affect the occurrence and development of RA. However, the reciprocal interaction between the components of the gut microbiota and their microbial metabolites with distinct ICs and how this interaction may impact the development of RA are not well studied. Therefore, a better understanding of the gut microbiota, ICs, and their interactions might improve our knowledge of the mechanisms by which the gut microbiota contribute to RA and facilitate the further development of novel therapeutic approaches. In this review, we have summarized the roles of the gut microbiota in the immunopathogenesis of RA, especially the interactions between the gut microbiota and ICs, and further discussed the strategies for treating RA by targeting/regulating the gut microbiota.

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Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Cited by 40 publications

References 43 publications

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

Amino Acid Metabolism in Rheumatoid Arthritis: Friend or Foe?

Regional Differences in the Gut Microbiota and Gut-Associated Immunologic Factors in the Ileum and Cecum of Rats With Collagen-Induced Arthritis

Interactions between Gut Microbiota and Immunomodulatory Cells in Rheumatoid Arthritis

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