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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
Source :
International Journal of Molecular Sciences. Aug2020, Vol. 21 Issue 16, p5713-5713. 1p.
Publication Year :
2020

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16616596
Volume :
21
Issue :
16
Database :
Academic Search Index
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
145416813
Full Text :
https://doi.org/10.3390/ijms21165713