Physiology and Pathology of Autoimmune Diseases: Role of CD4+ T cells in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by synovial inlammation leading to bone erosion and to systemic manifestations in patients with long RA duration. Although the aetiology is unknown, several observations make currently clear that CD4 T cells play a key role in the pathogenesis: (1) RA associates with certain polymorphisms of HLA class II molecules, and (2) the repertoire and aging of CD4 T cells as well as the intracellular signalling mediating CD4 T cell activation are altered in RA patients. We describe herein the alterations found in CD4 T cells and the role of these cells in the development and progression of RA.

Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint

“…In the model we consider only resident fibroblasts and resident macrophages, and not subsets of these populations or other immune cell types. Further immune cells can play a role in the progression of rheumatoid arthritis such as T cells and B cells [17, 64]. These immune cells, their mechanisms and their interactions with components of the joint could be included within the model using the same methods as those used to incorporate fibroblasts and macrophages.…”

“…For example, the role of chondrocytes and the highly organised extracellular matrix (ECM) within cartilage [17, 19, 28, 35] could be considered. Furthermore, the (im)balance between osteoclasts, which degrade bone, and osteoblasts, which produce bone, within the bone [17, 28, 35] could also be investigated in the RA context further. To incorporate these features we could consider method similar to those used to previously model cartilage growth [93] or bone remodelling [3, 16, 32, 43, 49, 55].…”

“…Following the onset of RA, the synovial membrane expands through various inflammatory mechanisms, this growing membrane is known as a ‘pannus’ and can behave similarly to a locally invasive tumour spreading within the joint [79]. Through both an increase in the proliferation of FLSs and the infiltration of immune cells, such as bone-marrow derived macrophages, the synovial membrane can expand to around 10-20 cells in thickness [17, 29, 35, 79, 97]. In this work, we focus on resident macrophages, or macrophagelike synoviocytes, and resident fibroblasts, or fibroblast-like synoviocytes, which form the majority of the pannus.…”

“…Cartilage is a connective tissue consisting of chondrocytes which produce a dense extra cellular matrix (ECM). Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) mediate cartilage destruction and are produced by B cells, FLSs and macrophages in the RA setting [17, 19, 28, 35, 105]. Cells within the pannus can also stimulate cartilage degradation via direct cell contact mechanisms [19, 29].…”

A Computational Modeling Framework to Analyze Synovial-Tissue Based Drug Targets and Diagnostic Biomarkers in Rheumatoid Arthritis

“…CD4 ⎯ (macrophage) → TNF-α Castro-Sanchez and Roda-Navarro designed a model that demonstrated the role of CD4 T cells in the expression of TNF-α and the exacerbation of RA (33).…”