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Increased frequency of CD16+ monocytes and the presence of activated dendritic cells in salivary glands in primary Sjögren’s Syndrome
  1. Manon E. Wildenberg (m.wildenberg{at}erasmusmc.nl)
  1. Erasmus MC, Netherlands
    1. Jojanneke MC Welzen-Coppens (j.coppens{at}erasmusmc.nl)
    1. Erasmus MC, Netherlands
      1. Cornelia G van Helden-Meeuwsen (c.vanhelden-meeuwsen{at}erasmusmc.nl)
      1. Erasmus MC, Netherlands
        1. Hendrika Bootsma (h.bootsma{at}int.umcg.nl)
        1. UMC Groningen, Netherlands
          1. Arjan Vissink (a.vissink{at}kchir.umcg.nl)
          1. UMC Groningen, Netherlands
            1. Nico van Rooijen (nvanrooijen{at}clodronateliposomes.org)
            1. VUMC, Netherlands
              1. Joop P van de Merwe (j.vandemerwe{at}erasmusmc.nl)
              1. Erasmus MC, Netherlands
                1. Hemmo A Drexhage (h.drexhage{at}erasmusmc.nl)
                1. Erasmus MC, Netherlands
                  1. Marjan A Versnel (m.versnel{at}erasmusmc.nl)
                  1. Erasmus MC, Netherlands

                    Abstract

                    Objectives: In the salivary glands of primary Sjögren’s Syndrome (pSjS) patients an accumulation of dendritic cells (DC) is seen, which is thought to play a role in stimulating the local inflammation. Aberrancies in subsets of monocytes, generally considered the blood precursors for DC, may play a role in this accumulation of DC. This study aimed at determining the level of mature CD14lowCD16+ monocytes in pSjS and their contribution to the accumulation of DC in pSjS.

                    Methods: Levels of mature and immature monocytes in pSjS patients (n=19) and controls (n=15) were analyzed by flow cytometry. The reverse transmigration system was used for generation of DC generated from monocyte subsets. The phenotype of DC in pSjS salivary glands was analyzed using immunohistochemistry. In vivo tracking of monocyte subsets was performed in a mouse model.

                    Results: Increased levels of mature CD14lowCD16+ monocytes were found in pSjS patients (14.5% +/- 5.5 vs 11.4% +/- 3.4). These cells showed a normal expression of chemokine receptor and adhesion molecules. Mature monocytes partly developed into DC-LAMP+ (19.6% +/- 7.5) and CD83+ (16% +/- 9%) DC, markers also expressed by DC in pSjS salivary glands. Monocyte tracking in the NOD mouse showed that the homologue population of mature mouse monocytes migrated to the salivary glands, and preferentially developed into CD11c+ DC in vivo.

                    Conclusion: Mature monocytes are increased in pSjS and both patient and mouse data support a model where this mature monocyte subset migrates to the salivary glands and develops into DC.

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