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- Title
Human Lymph Node Stromal Cells Have the Machinery to Regulate Peripheral Tolerance during Health and Rheumatoid Arthritis.
- Authors
Hähnlein, Janine S.; Nadafi, Reza; Jong, Tineke A. de; Semmelink, Johanna F.; Remmerswaal, Ester B. M.; Safy, Mary; Lienden, Krijn P. van; Maas, Mario; Gerlag, Danielle M.; Tak, Paul P.; Mebius, Reina E.; Wähämaa, Heidi; Catrina, Anca I.; G. M. van Baarsen, Lisa
- Abstract
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.
- Subjects
PROGRAMMED cell death 1 receptors; STROMAL cells; RHEUMATOID arthritis; LYMPH nodes; ANTIGEN presentation; IMMUNOREGULATION
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 16, p5713
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21165713