scholarly journals Human Lymph Node Stromal Cells Have the Machinery to Regulate Peripheral Tolerance during Health and Rheumatoid Arthritis

2020 ◽  
Vol 21 (16) ◽  
pp. 5713
Author(s):  
Janine S. Hähnlein ◽  
Reza Nadafi ◽  
Tineke A. de Jong ◽  
Johanna F. Semmelink ◽  
Ester B. M. Remmerswaal ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Antigen Presentation ◽  
Stromal Cells ◽  
Immune Modulation ◽  
Ex Vivo ◽  
Human Leukocyte ◽  
Interferon Γ ◽  
Peripheral Tolerance ◽  
Lymph Node Stromal Cells

Background: In rheumatoid arthritis (RA) the cause for loss of tolerance and anti-citrullinated protein antibody (ACPA) production remains unidentified. Mouse studies showed that lymph node stromal cells (LNSCs) maintain peripheral tolerance through presentation of peripheral tissue antigens (PTAs). We hypothesize that dysregulation of peripheral tolerance mechanisms in human LNSCs might underlie pathogenesis of RA. Method: Lymph node (LN) needle biopsies were obtained from 24 RA patients, 23 individuals positive for RA-associated autoantibodies but without clinical disease (RA-risk individuals), and 14 seronegative healthy individuals. Ex vivo human LNs from non-RA individuals were used to directly analyze stromal cells. Molecules involved in antigen presentation and immune modulation were measured in LNSCs upon interferon γ (IFNγ) stimulation (n = 15). Results: Citrullinated targets of ACPAs were detected in human LN tissue and in cultured LNSCs. Human LNSCs express several PTAs, transcription factors autoimmune regulator (AIRE) and deformed epidermal autoregulatory factor 1 (DEAF1), and molecules involved in citrullination, antigen presentation, and immunomodulation. Overall, no clear differences between donor groups were observed with exception of a slightly lower induction of human leukocyte antigen-DR (HLA-DR) and programmed cell death 1 ligand (PD-L1) molecules in LNSCs from RA patients. Conclusion: Human LNSCs have the machinery to regulate peripheral tolerance making them an attractive target to exploit in tolerance induction and maintenance.

scholarly journals Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Antonio P Baptista ◽  
Ramon Roozendaal ◽  
Rogier M Reijmers ◽  
Jasper J Koning ◽  
Wendy W Unger ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
Stromal Cells ◽  
Transplant Rejection ◽  
Mhc Ii ◽  
Self Antigen ◽  
Lymph Node Stromal Cells

Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8+ T cells and MHC-II-dependent anergy of CD4+ T cells. In this study, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of MHC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4+ as well as CD8+ T cells became activated, ultimately resulting in transplant rejection. MHC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.

OP0256 Changes of Microrna Expression in Lymph Node Stromal Cells of Rheumatoid Arthritis Patients

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 158.2-158
Author(s):  
C. Ospelt ◽  
J. Hähnlein ◽  
R.E. Gay ◽  
P.P. Tak ◽  
D.M. Gerlag ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Stromal Cells ◽  
Microrna Expression ◽  
Lymph Node Stromal Cells

scholarly journals OP0154 Altered lymph node stromal cells during the earliest phases of rheumatoid arthritis

2017 ◽  
Author(s):  
C Ospelt ◽  
E Karouzakis ◽  
J Hähnlein ◽  
JF Semmelink ◽  
RE Gay ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Stromal Cells ◽  
Lymph Node Stromal Cells

scholarly journals Molecular Characterization of Human Lymph Node Stromal Cells During the Earliest Phases of Rheumatoid Arthritis

2019 ◽  
Vol 10 ◽  
Author(s):  
Emmanuel Karouzakis ◽  
Janine Hähnlein ◽  
Cristoforo Grasso ◽  
Johanna F. Semmelink ◽  
Paul P. Tak ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Molecular Characterization ◽  
Stromal Cells ◽  
Human Lymph Node ◽  
Lymph Node Stromal Cells

scholarly journals Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis

2022 ◽  
Vol 8 ◽  
Author(s):  
Aoife M. O'Byrne ◽  
Tineke A. de Jong ◽  
Lisa G. M. van Baarsen
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Stromal Cells ◽  
Clinical Manifestations ◽  
Bone Destruction ◽  
Peripheral Tolerance ◽  
Unknown Etiology ◽  
Synovial Joint ◽  
Innovative Drug

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.

scholarly journals Author response: Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

2014 ◽  
Author(s):  
Antonio P Baptista ◽  
Ramon Roozendaal ◽  
Rogier M Reijmers ◽  
Jasper J Koning ◽  
Wendy W Unger ◽  
...  
Keyword(s):  
Lymph Node ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Stromal Cells ◽  
Class Ii ◽  
Author Response ◽  
Self Antigen ◽  
Lymph Node Stromal Cells
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