Brief CommunicationDecreased dendritic cell numbers but increased TLR9-mediated interferon-alpha production in first degree relatives of type 1 diabetes patients

- T1D patients and their relatives have decreased blood mDC and pDC numbers.
- T1D relatives produced an increased amount of IFN-alpha upon TLR9 ligand stimulation.
- Relatives with low genetic risk and negative autoantibodies produce lower IFN-alpha.

ObjectiveDendritic cells (DCs) play an important role in pathogenesis of autoimmunity, including type 1 diabetes (T1D). In this study, we investigated DC subpopulations and their responses to TLR stimulation in T1D patients and their relatives.MethodsWe analyzed the frequency of myeloid (mDCs) and plasmacytoid DCs (pDCs) in 97 T1D patients (69 onset, 28 long-term), 67 first-degree relatives, and 64 controls. We additionally tested the IFN-alpha production by pDCs upon stimulation with TLR 7, 8 and 9 agonists.ResultsA lower number of mDCs and pDCs were found in T1D patients and their relatives. Of all the tested TLR ligands, only stimulation with CpG 2216 induced IFN-alpha production that was the highest in T1D relatives, except of autoantibody-negative relatives bearing the protective haplotypes.ConclusionOur data demonstrate disturbances in DC number and function expressed most significantly in T1D relatives and point to a potential role of TLR9-induced IFN-alpha production in T1D development.