Immunomodulatory role of T helper cells in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps. Cite this article: Bone Joint Res 2022;11(7):426–438.

Advanced immunophenotyping: A powerful tool for immune profiling, drug screening, and a personalized treatment approach

“…The appropriate detection and activation of the different Th cell lineages are pivotal for studies elucidating the effects of immunomodulatory drugs since they are dysregulated in various autoimmune disorders and contribute to the pathogenesis of these diseases (8,11,12). In this context, particularly Th1, Th17, and Tfh cells have been linked to the pathophysiology of autoimmune conditions, such as RA, SLE, and MS; whereas Tregs and Th2 cells are considered to exert immune-suppressive functions (8,11,12,14). In the presented study we detected decreased proportions of Th2 and increased levels of Tfh, Tph and Tregs in RA patients compared to HCs, corresponding to current reports (8,(13)(14)(15).…”

“…Over the past decade, markers found in serum, plasma, and whole blood have been tested for their potential as biomarkers in autoimmunity (4)(5)(6). Previously, cellular biomarkers from Peripheral blood mononuclear cells (PBMCs) indicative of autoimmune disorders have moved into the focus of science (7)(8)(9)(10)(11)(12)(13)(14)(15). PBMCs consist of many different cell types with varying frequencies.…”

“…They function as drivers and regulators of physiological and pathological immune responses, which can lead to autoimmunity and inflammation (16). Alterations in PBMC subsets, and especially in T helper (Th) cells are characteristic of various autoimmune disorders and contribute to the pathogenesis, for instance of RA, multiple sclerosis (MS), or systemic lupus erythematosus (SLE) (8,11,12). Several studies demonstrated, that patients suffering from autoimmune disease conditions exhibit elevated levels of antibody-secreting B cells and CD4 + memory T cells, respectively, compared to healthy individuals (17)(18)(19).…”

“…Several studies demonstrated, that patients suffering from autoimmune disease conditions exhibit elevated levels of antibody-secreting B cells and CD4 + memory T cells, respectively, compared to healthy individuals (17)(18)(19). Increased frequencies of distinct CD4 + T cell subsets, such as Th1, Th17, T follicular helper cells (Tfh), regulatory T cells (Treg), and CD4 + CD25 -Foxp3 + T cells, have been linked to aberrant immune responses (7)(8)(9)(10)(11)(12)(13)(14)(15). Hence, certain PBMC compartments might constitute promising cellular biomarkers for the application as clinical parameters, as shown for CD19 + B cell numbers as an indicator for RA relapse after B cell depletion therapy using Rituximab (20)(21)(22)(23).…”

Berberine inhibits RA-FLS cell proliferation and adhesion by regulating RAS/MAPK/FOXO/HIF-1 signal pathway in the treatment of rheumatoid arthritis

“…9 RA is a chronic autoimmune disease whose main clinical manifestations are synovitis and joint damage. [10][11][12] RA fibroblast-like synoviocytes (RA-FLSs) are highly specialized mesenchymal cells in sensitive joint synovium with strong invasive ability, and play an important role in the progression of RA. 13 RA-FLSs can secrete a variety of pathogenic mediators such as cytokines (tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-23) and chemokines (receptor activator of nuclear factor kappa-Β ligand (RANKL), granulocyte-macrophage colony stimulating factor, and matrix metalloproteinases (MMPs)).…”