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The draining lymph node in rheumatoid arthritis: current concepts and research perspectives.

Benaglio F, Vitolo B, Scarabelli M, Binda E, Bugatti S, Caporali R, Montecucco C, Manzo A - Biomed Res Int (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology and Translational Immunology Research Laboratories (LaRIT), Division of Rheumatology, IRCCS Policlinico S. Matteo Foundation/University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy.

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.

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Related in: MedlinePlus

Potential pathophysiologic changes of and interactions between the joint and draining LN in course of inflammatory arthritis. (a) Schematic representation of the main anatomic compartments within a noninflamed joint and a resting LN. (b) Hypothetical spectrum of interactive relationships between the joint and the draining LN in course of arthritis. Joint inflammation promotes local accumulation of immune cells, synovial tissue hypertrophy and structural damage through the differentiation/activation of osteoclasts. These changes can promote increased fluid and cell drainage to adjoining LN through the afferent lymphatic system. An efficient drainage activity (left diagram, blue-filled arrow) may exert a compensatory effect on joint pathology by promoting fluid and cell exit. As an additional (nonmutually exclusive) effect, it might also contribute to disease immune-pathology by favouring neoantigen delivery, local immune-reactivity and (auto)antibody production. In the left LN diagram of (b), these mechanisms, together with putative structural changes (hypertrophy, cell accumulation, follicular hyperplasia, and increased vascularity) characterizing the challenged LN are shown. On the other side, a defective or insufficient drainage activity to the node (right diagram, blue-dashed arrow) may directly contribute to accumulation of inflammatory cells in the joint, promoting local cell activation and enhancing local disease (right hand side diagram of the joint).
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fig1: Potential pathophysiologic changes of and interactions between the joint and draining LN in course of inflammatory arthritis. (a) Schematic representation of the main anatomic compartments within a noninflamed joint and a resting LN. (b) Hypothetical spectrum of interactive relationships between the joint and the draining LN in course of arthritis. Joint inflammation promotes local accumulation of immune cells, synovial tissue hypertrophy and structural damage through the differentiation/activation of osteoclasts. These changes can promote increased fluid and cell drainage to adjoining LN through the afferent lymphatic system. An efficient drainage activity (left diagram, blue-filled arrow) may exert a compensatory effect on joint pathology by promoting fluid and cell exit. As an additional (nonmutually exclusive) effect, it might also contribute to disease immune-pathology by favouring neoantigen delivery, local immune-reactivity and (auto)antibody production. In the left LN diagram of (b), these mechanisms, together with putative structural changes (hypertrophy, cell accumulation, follicular hyperplasia, and increased vascularity) characterizing the challenged LN are shown. On the other side, a defective or insufficient drainage activity to the node (right diagram, blue-dashed arrow) may directly contribute to accumulation of inflammatory cells in the joint, promoting local cell activation and enhancing local disease (right hand side diagram of the joint).

Mentions: The data presented in the previous sections of this review support the role of the LN as a potential relevant component of arthritis pathology, opening the attracting perspective of extending our research focus to this anatomic compartment as a complementary tool for the implementation of current prognostic biomarkers, the definition of preventive strategies, as well as the development of novel therapeutic approaches (Figure 1). The same data, however, also point at the significant gaps that still characterize current knowledge in the field with specific reference to the biology, functional dynamics, and hierarchical role of the LN compartment in human disease, both in its preclinical phases and in its established stage.


The draining lymph node in rheumatoid arthritis: current concepts and research perspectives.

Benaglio F, Vitolo B, Scarabelli M, Binda E, Bugatti S, Caporali R, Montecucco C, Manzo A - Biomed Res Int (2015)

Potential pathophysiologic changes of and interactions between the joint and draining LN in course of inflammatory arthritis. (a) Schematic representation of the main anatomic compartments within a noninflamed joint and a resting LN. (b) Hypothetical spectrum of interactive relationships between the joint and the draining LN in course of arthritis. Joint inflammation promotes local accumulation of immune cells, synovial tissue hypertrophy and structural damage through the differentiation/activation of osteoclasts. These changes can promote increased fluid and cell drainage to adjoining LN through the afferent lymphatic system. An efficient drainage activity (left diagram, blue-filled arrow) may exert a compensatory effect on joint pathology by promoting fluid and cell exit. As an additional (nonmutually exclusive) effect, it might also contribute to disease immune-pathology by favouring neoantigen delivery, local immune-reactivity and (auto)antibody production. In the left LN diagram of (b), these mechanisms, together with putative structural changes (hypertrophy, cell accumulation, follicular hyperplasia, and increased vascularity) characterizing the challenged LN are shown. On the other side, a defective or insufficient drainage activity to the node (right diagram, blue-dashed arrow) may directly contribute to accumulation of inflammatory cells in the joint, promoting local cell activation and enhancing local disease (right hand side diagram of the joint).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352497&req=5

fig1: Potential pathophysiologic changes of and interactions between the joint and draining LN in course of inflammatory arthritis. (a) Schematic representation of the main anatomic compartments within a noninflamed joint and a resting LN. (b) Hypothetical spectrum of interactive relationships between the joint and the draining LN in course of arthritis. Joint inflammation promotes local accumulation of immune cells, synovial tissue hypertrophy and structural damage through the differentiation/activation of osteoclasts. These changes can promote increased fluid and cell drainage to adjoining LN through the afferent lymphatic system. An efficient drainage activity (left diagram, blue-filled arrow) may exert a compensatory effect on joint pathology by promoting fluid and cell exit. As an additional (nonmutually exclusive) effect, it might also contribute to disease immune-pathology by favouring neoantigen delivery, local immune-reactivity and (auto)antibody production. In the left LN diagram of (b), these mechanisms, together with putative structural changes (hypertrophy, cell accumulation, follicular hyperplasia, and increased vascularity) characterizing the challenged LN are shown. On the other side, a defective or insufficient drainage activity to the node (right diagram, blue-dashed arrow) may directly contribute to accumulation of inflammatory cells in the joint, promoting local cell activation and enhancing local disease (right hand side diagram of the joint).
Mentions: The data presented in the previous sections of this review support the role of the LN as a potential relevant component of arthritis pathology, opening the attracting perspective of extending our research focus to this anatomic compartment as a complementary tool for the implementation of current prognostic biomarkers, the definition of preventive strategies, as well as the development of novel therapeutic approaches (Figure 1). The same data, however, also point at the significant gaps that still characterize current knowledge in the field with specific reference to the biology, functional dynamics, and hierarchical role of the LN compartment in human disease, both in its preclinical phases and in its established stage.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology and Translational Immunology Research Laboratories (LaRIT), Division of Rheumatology, IRCCS Policlinico S. Matteo Foundation/University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy.

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.

Show MeSH
Related in: MedlinePlus