Circulating dendritic cells of MS patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors

Dendritic cells (DC) are innate immune cells and may play a role in the pathogenesis of MS. Due to their specialised antigen-presenting capacity; DCs provide an important link between the innate and the adaptive immune system. Therefore, DCs are involved in regulating the balance between immunity and tolerance.

This study looked at characterising circulating DC populations in MS and to see if there is any contribution of MS-associated genetic risk factors to DCs. Analysis was carried out on conventional (cDCs) and plasmacytoid DCs (pDCs) in peripheral blood of people with MS and age-matched controls. The researchers found that there was a decrease in pDCs in people with chronic progressive MS compared to RRMS and healthy controls. No difference was found in cDCs frequency between the different groups.

In the second part of this study, people with MS were genotyped for HLA-DRB1*1501 and IL-7Rα variants to see if these MS-associated genetic risk factors affect the DC compartment. HLA-DRB1*1501 carriers have a 3-4 times higher relative risk of developing MS. While IL-7Rα is one of the first non-HLA gene loci linked to MS susceptibility and is the gene for interleukin (IL)-7 receptor α-chain, IL-7 signalling is pivotal for central T cell development and homeostasis. HLA-DRB1*1501+ MS patients and patients not carrying the protective IL-7Rα haplotype 2 have decreased frequencies of circulating cDCs and pDCs respectively. There was enhanced production of IL-12p70 upon TLR (Toll-like receptors) ligation indicating that cDCs of people with RRMS are in a more activated state when compared to controls. There was also an increased expression of the migratory molecules CCR5 and CCR7. Based on these results, DCs are in a pro-inflammatory state in MS and are affected by genetic risk factors.

Authors: Thewissen K, Nuyts AH
Source: Mult Scler. 2013 Sep 23. [Epub ahead of print]

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