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Distinct activation of primary human BDCA1+ dendritic cells upon interaction with stressed or infected β cells.

Authors :
Schulte, B. M.
Kers‐Rebel, E. D.
Bottino, R.
Piganelli, J. D.
Galama, J. M. D.
Engelse, M. A.
de Koning, E. J. P.
Adema, G. J.
Source :
Clinical & Experimental Immunology; Jun2016, Vol. 184 Issue 3, p293-307, 15p, 6 Graphs
Publication Year :
2016

Abstract

Derailment of immune responses can lead to autoimmune type 1 diabetes, and this can be accelerated or even induced by local stress caused by inflammation or infection. Dendritic cells (DCs) shape both innate and adaptive immune responses. Here, we report on the responses of naturally occurring human myeloid BDCA1<superscript>+</superscript> DCs towards differentially stressed pancreatic β cells. Our data show that BDCA1<superscript>+</superscript> DCs in human pancreas-draining lymph node (pdLN) suspensions and blood-derived BDCA1<superscript>+</superscript> DCs both effectively engulf β cells, thus mimicking physiological conditions. Upon uptake of enterovirus-infected, but not mock-infected cells, BDCA1<superscript>+</superscript> DCs induced interferon (IFN)-α/β responses, co-stimulatory molecules and proinflammatory cytokines and chemokines. Notably, induction of stress in β cells by ultraviolet irradiation, culture in serum-free medium or cytokine-induced stress did not provoke strong DC activation, despite efficient phagocytosis. DC activation correlated with the amount of virus used to infect β cells and required RNA within virally infected cells. DCs encountering enterovirus-infected β cells, but not those incubated with mock-infected or stressed β cells, suppressed T helper type 2 (Th2) cytokines and variably induced IFN-γ in allogeneic mixed lymphocyte reaction (MLR). Thus, stressed β cells have little effect on human BDCA1<superscript>+</superscript> DC activation and function, while enterovirus-infected β cells impact these cells significantly, which could help to explain their role in development of autoimmune diabetes in individuals at risk. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00099104
Volume :
184
Issue :
3
Database :
Complementary Index
Journal :
Clinical & Experimental Immunology
Publication Type :
Academic Journal
Accession number :
115423339
Full Text :
https://doi.org/10.1111/cei.12779