Dendritic cells, T cells and their interaction in rheumatoid arthritis

Wehr, Pascale; Purvis, Harriet A.; Law, Soi Cheng; Thomas, Ranjeny

doi:10.1111/cei.13256

Cited by 127 publications

(75 citation statements)

References 158 publications

(273 reference statements)

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“…In general, lymphoid tissue in healthy individuals, RA-risk individuals and early-RA patients contains more mDCs than pDCs (Figure 1). This suggests that mDCs may play an important role in the initiation of the disease by presenting (auto)antigens to CD8 T cells [36,37,38]. Related to this, our data show that in early RA, mDCs localized in T cell areas and in close proximity to B cells, suggesting that mDCs may form a complex with B and T cells and activate both [39].…”

Section: Discussionsupporting

confidence: 64%

Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals

Ramwadhdoebé

Ramos

Maijer

et al. 2019

Cells

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Lymph nodes (LNs) are highly organized structures where specific immune responses are initiated by dendritic cells (DCs). We investigated the frequency and distribution of human myeloid (mDCs) and plasmacytoid (pDCs) in LNs and blood during the earliest phases of rheumatoid arthritis (RA). We included 22 RA-risk individuals positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies, 16 biological-naïve RA patients and 8 healthy controls (HCs). DC subsets (CD1c+ mDCs and CD304+ pDCs) in LN tissue and paired peripheral blood were analyzed using flow cytometry and confocal microscopy. In blood of RA patients a significant decreased frequency of pDCs was found, with a similar trend for mDCs. In contrast, mDC frequencies were higher in RA compared with HCs and RA-risk individuals, especially in LN. Frequency of mDCs seemed higher in LNs compared to paired blood samples in all donors, while pDCs were higher in LNs only in RA patients. As expected, both mDCs and pDCs localized mainly in T-cell areas of LN tissue. In conclusion, compared with RA-risk individuals, mDCs and pDCs were enriched in the LN tissue of early-RA patients, while their frequency in RA-risk individuals was comparable to HCs. This may suggest that other antigen-presenting cells are responsible for initial breaks of tolerance, while mDCs and pDCs are involved in sustaining inflammation.

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Section: Discussionsupporting

confidence: 64%

Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals

Ramwadhdoebé

Ramos

Maijer

et al. 2019

Cells

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“…During homeostasis, dendritic cells (DCs) are involved in the maintenance of immune regulation and tolerance. However, in RA by presenting self-peptides, they trigger differentiation and activation of the auto-reactive T cells as well as innate immune effector functions [14]. In RA patients, increased numbers of DCs are present in the synovial fluid and tissues.…”

Section: Dendritic Cellsmentioning

confidence: 99%

Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis

Fang

Zhou

Nandakumar

2020

Mediators of Inflammation

143

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Rheumatoid arthritis is a chronic autoimmune syndrome associated with several genetic, epigenetic, and environmental factors affecting the articular joints contributing to cartilage and bone damage. Although etiology of this disease is not clear, several immune pathways, involving immune (T cells, B cells, dendritic cells, macrophages, and neutrophils) and nonimmune (fibroblasts and chondrocytes) cells, participate in the secretion of many proinflammatory cytokines, chemokines, proteases (MMPs, ADAMTS), and other matrix lysing enzymes that could disturb the immune balance leading to cartilage and bone damage. The presence of autoantibodies preceding the clinical onset of arthritis and the induction of bone erosion early in the disease course clearly suggest that initiation events damaging the cartilage and bone start very early during the autoimmune phase of the arthritis development. During this process, several signaling molecules (RANKL-RANK, NF-κB, MAPK, NFATc1, and Src kinase) are activated in the osteoclasts, cells responsible for bone resorption. Hence, comprehensive knowledge on pathogenesis is a prerequisite for prevention and development of targeted clinical treatment for RA patients that can restore the immune balance improving clinical therapy.

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“…RA is a chronic, systemic autoimmune disease characterized by inflammation and destruction of the joints and progressive disability. Infiltrated cells including granulocytes, monocytes/macrophages, natural killer (NK) cells, B cells, and especially T cells have been implicated in the pathogenesis of RA by producing many chemokines and proinflammatory cytokines (Drexler et al, 2008; Mellado et al, 2015, Wehr et al, 2018; Yap et al, 2018). Although the roles of these inflammatory cells is poorly understood, blocking or inhibiting these cells that secrete proinflammatory cytokines relieves the symptoms of RA (Bullock et al, 2018; Mahajan and Mikuls, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Patients are usually administered long-term disease-modifying anti-rheumatic drugs, such as methotrexate (MTX) (Yap et al, 2018). Many immune cells, such as T cells, B cells, and macrophages, play crucial roles in the pathogenesis of RA via stimulating proinflammatory cytokine and chemokine release (Silverman and Carson, 2003; Drexler et al, 2008; Iwamoto et al, 2008; Wang et al, 2011; Mellado et al, 2015; Sun et al, 2018; Wehr et al, 2018; Yap et al, 2018); therefore, targeting immune cells or proinflammatory cytokines is beneficial for RA patients (Asquith et al, 2015; Bullock et al, 2018; Littlejohn and Monrad, 2018; Mahajan and Mikuls, 2018; Zhao et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Sphingosine-1-Phosphate Receptor Subtype 1 (S1P1) Modulator IMMH001 Regulates Adjuvant- and Collagen-Induced Arthritis

Jin

et al. 2019

Front. Pharmacol.

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Sphingosine-1-phosphate receptor subtype 1 (S1P1) is essential for lymphocyte egress from lymphoid organs into systemic circulation and provides a well-defined drug target for autoimmune disorders. IMMH001, also called SYL930, is a specific S1P1/S1P4/S1P5 modulator. Here, we investigated the potential therapeutic effect of IMMH001 on rheumatoid arthritis (RA). IMMH001 rendered periphery blood lymphocytes insensitive to the egress signal from secondary lymphoid organs. Importantly, in both rat adjuvant-induced arthritis and collagen-induced arthritis models, IMMH001 treatment significantly inhibited the progression of RA and RA-associated histological changes in the joints of Sprague-Dawley rats, including hind paw swelling and arthritic index, and thus reduced the pathological score. Furthermore, IMMH001 markedly decreased proinflammatory cytokine and chemokine release from the damaged joints. These data demonstrated that IMMH001 is a promising drug candidate for RA treatment.

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Dendritic cells, T cells and their interaction in rheumatoid arthritis

Cited by 127 publications

References 158 publications

Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals

Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals

Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis

Sphingosine-1-Phosphate Receptor Subtype 1 (S1P1) Modulator IMMH001 Regulates Adjuvant- and Collagen-Induced Arthritis

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