Citrullinated human fibrinogen triggers arthritis through an inflammatory response mediated by IL-23/IL-17 immune axis

Author(s)

Saraiva, Andre Lopes ; Peres, Raphael Sanches ; Veras, Flavio Protasio ; Talbot, Jhimmy ; de Lima, Kalil Alves ; Mesquita Luiz, Joao Paulo ; Cunha, Thiago Mattar ; Louzada-Junior, Paulo ; Cunha, Fernando Queiroz ; Alves-Filho, Jose Carlos

• Document type: Journal article
• Source: International Immunopharmacology; v. 101, p. 8-pg., 2021-12-01.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that causes joint destruction. Although its etiology remains unknown, citrullinated proteins have been considered as an auto-antigen able to trigger an inflammatory response in RA. Herein, we modified the classical antigen-induced arthritis (AIA) model by using citrullinated human plasma fibrinogen (hFIB) as an immunogen to investigate the mechanism of inflammation-driven joint damage by citrullinated hFIB in C57BL/6 mice. We found that hFIB-immunized mice showed high serum levels of anti-citrullinated peptides antibodies (ACPAs). Moreover, hFIB immunized mice showed increased mechanical hyperalgesia, massive leukocyte infiltration, high levels of inflammatory mediators, and progressive joint damage after the intra-articular challenge with citrullinated hFIB. Interestingly, hFIB-induced arthritis was dependent on IL-23/IL-17 immune axis-mediated inflammatory responses since leukocyte infiltration and mechanical hyperalgesia were abrogated in Il17ra / and Il23a / mice. Thus, we have characterized a novel model of experimental arthritis suitable to investigate the contribution of ACPAs and Th17 cell-mediated immune response in the pathogenesis of RA. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 11/12671-1 - The role of succinate and its receptor GPR91 on the pathophysiology of experimental arthritis
• Grantee: André Luis Lopes Saraiva
• Support Opportunities: Scholarships in Brazil - Doctorate