The intervention of intestinal Wnt/β-catenin pathway alters inflammation and disease severity of CIA.

Abstract

Autoreactive T cell is one of the leading causes of immunological tolerance defects in the chronic inflammatory lesions of rheumatoid arthritis (RA). There have been several extracellular signals and intracellular pathways reported in regulating this process but largely remain unknown yet. In this study, we explored the roles of intestinal Wnt/β-catenin on disease severity during collagen-induced arthritis model (CIA), an animal model of RA. We first testified the activity pattern Wnt/β-catenin shifted by intragastric administration of LiCl and DKK-1 in the intestine by real-time PCR and WB analysis. The arthritis scores showing the disease severity in the DKK-1 group was significantly ameliorated compared with the control group at the late stage of the disease, while in the LiCl group, the scores were significantly elevated which was consistent with pathology score analysis of H&E staining. Next, ELISA was performed and showed that TNF-α and IL-17 in the LiCl group were significantly higher than that of the control group. IL-10 in the DKK-1 group was significantly higher than that in the LiCl-1 group and control group, P < 0.05. Flow cytometry of spleen T cells differentiation ratio showed that: Th1 from the DKK-1 and LiCl groups and Th17 from the LiCl group was significantly different from that of the blank model group, P < 0.05. Finally, we explored the effects of intestinal Wnt/β-catenin on T cell differentiation regulator ROR-γt and TCF1 and found that both transcription factors were up-regulated in the LiCl group. Together, these data suggested the pro-information role of Wnt/β-catenin pathway from the intestine in the CIA mouse, implying its use as a potential therapeutic target for the treatment of inflammatory diseases such as RA.

• Authors: Weixing Tan, Yang Qiu, Ning Chen, Jie Gao, Jingjing Liang, Yu Liu, Dongbao Zhao
• Journal: Immunologic research (Immunol Res) Vol. 69 Issue 4 Pg. 323-333 (08 2021) ISSN: 1559-0755 [Electronic] United States
• PMID: 34037945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Cytokines
• Hepatocyte Nuclear Factor 1-alpha
• Hnf1a protein, mouse
• Intercellular Signaling Peptides and Proteins
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Rorc protein, mouse
• Lithium Chloride

Topics

• Animals
• Arthritis, Experimental (genetics, immunology, pathology)
• Cytokines (immunology)
• Gene Expression
• Hepatocyte Nuclear Factor 1-alpha (immunology)
• Intercellular Signaling Peptides and Proteins (administration & dosage)
• Intestines (immunology)
• Joints (pathology)
• Lithium Chloride (administration & dosage)
• Male
• Mice, Inbred DBA
• Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics, immunology)
• Severity of Illness Index
• T-Lymphocytes (immunology)
• Tarsal Bones (pathology)
• Wnt Signaling Pathway
• Mice