The Draining Lymph Node in Rheumatoid Arthritis: Current Concepts and Research Perspectives

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of unknown aetiology, leading to progressive damage of bone and cartilage with functional impairment and disability. Whilst the synovial membrane represents the epicentre of the immune-inflammatory process, there is growing evidence indicating the potential involvement of additional anatomical compartments, such as the lung, bone marrow, and secondary lymphoid tissues. Draining lymph nodes represent the elective site for tissue immune-surveillance, for the generation of adaptive immune responses and a candidate compartment for the maintenance of peripheral tolerance. Despite the precise role of the juxta- and extra-articular lymph node stations in the pathogenesis of RA remaining poorly defined, several lines of research exploiting new technological approaches are now focusing on their assessment as a potential new source of pathobiologic information, biomarkers, and complementary therapeutic targets. In this review we present an updated overview of the main concepts driving lymph node research in RA, highlighting the most relevant findings, current hypothesis, and translational perspectives.

Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis

“…Mice that were selectively deficient in GCs are almost fully protected against CIA, whereas they are fully susceptible to collagen antibody-induced arthritis 17 . Following the induction of CIA GCs develop in inflamed joint tissues and secondary lymphoid tissues, including the lymph nodes draining inflamed joints and adjacent tissues (dLNs), often referred to as reactive lymph nodes 26 . An accumulating body of evidence suggests an important role of dLNs in the development and progression of CIA and RA trough cross-talk with the inflamed tissues, so peripheral tissues and their dLNs operate as a functional pathogenic unit 26 .…”

“…Following the induction of CIA GCs develop in inflamed joint tissues and secondary lymphoid tissues, including the lymph nodes draining inflamed joints and adjacent tissues (dLNs), often referred to as reactive lymph nodes 26 . An accumulating body of evidence suggests an important role of dLNs in the development and progression of CIA and RA trough cross-talk with the inflamed tissues, so peripheral tissues and their dLNs operate as a functional pathogenic unit 26 . Of note, Th cells from GCs referred to as follicular helper T (Tfh) cells critically contribute to the proliferation of (auto)antigen-primed GC B cells, isotype switching, and their somatic hypermutations leading to the generation of long-lived plasma cells and memory B cells 27 .…”

Targeting Suppressive Oligonucleotide to Lymph Nodes Inhibits Toll-like Receptor-9-Mediated Activation of Adaptive Immunity

“…Strengthening activation of innate immune system and thereby modifying the adaptive immune responses has long been considered in clinic in the treatment of cancer, allergy and infections (1,2). In parallel with the discovery of CpG ODN in stimulating TLR-9 and eliciting potent antigen-specific immunity, it was found activation of the innate immunity through TLR such as TLR-9 could lead to deleterious immune responses that resulted in destruction of self-tissues.…”

“…Toll-like receptors (TLRs) are highly conservative transmembrane receptors which play a key role in the early detection of pathogen and subsequent activation of the adaptive immune response (1,2). TLRs recognize specific pathogen-associated molecular patterns (PAMPs) associated with microbial pathogens, as well as a number of endogenous ligands such as selfprotein, lipids, and nucleic acids (1,2).…”

“…TLRs recognize specific pathogen-associated molecular patterns (PAMPs) associated with microbial pathogens, as well as a number of endogenous ligands such as selfprotein, lipids, and nucleic acids (1,2). In addition to pathogen sensing and clearance, accumulating evidence demonstrates that endogenous ligand-mediated signaling through TLR is involved in the pathogenesis of various autoimmune diseases (3–9), such as systemic lupus erythematosus (SLE) (6) and rheumatoid arthritis (RA) (8).…”