scholarly journals P112 Studying cellular senescence in human lymph node stromal cells during the earliest phases of rheumatoid arthritis

2019 ◽  
Author(s):  
TA De Jong ◽  
AL Timmerman ◽  
JF Semmelink ◽  
JS Hähnlein ◽  
LG van Baarsen
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Cellular Senescence ◽  
Stromal Cells ◽  
Human Lymph Node ◽  
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 POS0391 ASSESSING SENESCENT HUMAN LYMPH NODE STROMAL CELLS DURING RHEUMATOID ARTHRITIS DEVELOPMENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 425.2-425
Author(s):  
T. de Jong ◽  
J. W. Bolt ◽  
J. F. Semmelink ◽  
L. van Baarsen
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Damage ◽  
Lymph Node ◽  
Cell Size ◽  
Cellular Senescence ◽  
Stromal Cells ◽  
Healthy Controls ◽  
Expression Levels ◽  
Systemic Autoimmunity ◽  
Lymph Node Stromal Cells

Background:Cellular senescence is a state of proliferation arrest of cells. The persistence and accumulation of senescent cells has been implicated in the pathogenesis of age-related diseases like rheumatoid arthritis (RA). Clinical disease is preceded by loss of immune tolerance and autoimmunity. Lymph node stromal cells (LNSC) are important regulators of this tolerance. Therefore, senescent LNSC may affect tolerance and the development of systemic autoimmunity.Objectives:To determine the extent of cellular senescence of LNSC during early phases of systemic autoimmunity.Methods:We included individuals with arthralgia without any evidence of arthritis who were positive for IgM rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA; RA-risk group), early arthritis patients (ACR/EULAR 2010 criteria; disease duration < 1 year) and seronegative healthy controls. All study subjects underwent ultrasound-guided inguinal lymph node biopsy. LNSC were isolated and cultured from freshly collected lymph node needle biopsies and passages 0-9 were used for experiments. Cellular senescence was assessed by measuring cell size, granularity, autofluorescence, senescence-associated gene expression levels, DNA damage and senescence-associated β-galactosidase (SA β-gal) activity.Results:Preliminary flow cytometry data shows that the cell size and autofluorescence of LNSC from RA patients (n=11) and RA-risk individuals (n=7) is increased compared with healthy LNSC (n=7), while granularity was specifically increased in LNSC from RA patients (n=9). Initial stainings indicate higher SA β-gal activity and more DNA damage in LNSC from RA-risk (n=3) and RA patients (n=4) compared with healthy controls (n=3). Expression levels of senescence-associated genes such as p21 and p53 were significantly higher in LNSC from RA patients compared with healthy controls (n=6 per group).Conclusion:These preliminary findings suggest senescence already in early RA and provide a rationale for investigating the consequence of senescent LNSC on immune cell responsesDisclosure of Interests:None declared

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 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 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

A8.17 Expression of the autoimmune regulator aire in human lymph node stromal cells

2014 ◽  
Vol 73 (Suppl 1) ◽  
pp. A82.3-A83 ◽  
Author(s):  
J Hähnlein ◽  
T H Ramwadhdoebe ◽  
J F Semmelink ◽  
K I Maijer ◽  
I. Y. Choi ◽  
...  
Keyword(s):  
Lymph Node ◽  
Stromal Cells ◽  
Autoimmune Regulator ◽  
Human Lymph Node ◽  
Lymph Node Stromal Cells

scholarly journals O008 Altered lymph node stromal cells during the earliest phases of rheumatoid arthritis

2018 ◽  
Author(s):  
C Ospelt ◽  
E Karouzakis ◽  
J Hähnlein ◽  
H Semmelink ◽  
R Gay ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Stromal Cells ◽  
Lymph Node Stromal Cells
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