Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals.

T.H Ramwadhdoebe,M.I Ramos,K.P Van Lienden,K.I Maijer,D.M Gerlag,L.G.M Van Baarsen,P.P Tak,M.C Lebre,M Maas

doi:10.3390/cells8070756

T.H Ramwadhdoebe, M.I Ramos + Show 7 more

Open Access

https://doi.org/10.3390/cells8070756

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Abstract

Lymph nodes (LNs) are highly organized structures where specific immune responses are initiated by dendritic cells (DCs). We investigated the frequency and distribution of human myeloid (mDCs) and plasmacytoid (pDCs) in LNs and blood during the earliest phases of rheumatoid arthritis (RA). We included 22 RA-risk individuals positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies, 16 biological-naïve RA patients and 8 healthy controls (HCs). DC subsets (CD1c+ mDCs and CD304+ pDCs) in LN tissue and paired peripheral blood were analyzed using flow cytometry and confocal microscopy. In blood of RA patients a significant decreased frequency of pDCs was found, with a similar trend for mDCs. In contrast, mDC frequencies were higher in RA compared with HCs and RA-risk individuals, especially in LN. Frequency of mDCs seemed higher in LNs compared to paired blood samples in all donors, while pDCs were higher in LNs only in RA patients. As expected, both mDCs and pDCs localized mainly in T-cell areas of LN tissue. In conclusion, compared with RA-risk individuals, mDCs and pDCs were enriched in the LN tissue of early-RA patients, while their frequency in RA-risk individuals was comparable to HCs. This may suggest that other antigen-presenting cells are responsible for initial breaks of tolerance, while mDCs and pDCs are involved in sustaining inflammation.

Highlights

Dendritic cells (DCs) are professional antigen-presenting cells that specialize in the uptake of antigens and their transport from peripheral tissues to lymphoid organs
CD1c+ mDCs are Enriched in Human lymph nodes (LNs) Tissue of Early-rheumatoid arthritis (RA) Patients
As expected [7], the frequency of CD1c+ mDCs (Figure 1A) in peripheral blood mononuclear cells (PBMC) of early-RA patients was decreased compared with the healthy controls (HCs)

Summary

Introduction

Dendritic cells (DCs) are professional antigen-presenting cells that specialize in the uptake of antigens and their transport from peripheral tissues to lymphoid organs. Because of their capacity to stimulate naive T cells, DCs have a central role in the initiation of immune responses and are considered promising tools and targets for immunotherapy [1,2]. Two main DC subsets, myeloid or conventional (mDCs) and plasmacytoid (pDCs), with distinct functions have been the focus of much attention [6] In this respect, it was shown that mDCs and pDCs are decreased in RAperipheral blood [7], possibly due to their accumulation at the site of inflammation (the synovium) [8,9]. It is unclear whether in RA these DC subsets accumulate in the lymph nodes (LNs) where they may present (auto)antigens to T cells, and whether this accumulation can be found already in RA-risk individuals positive for autoantibodies

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