PMID- 26888163
OWN - NLM
STAT- MEDLINE
DCOM- 20170321
LR  - 20181113
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 184
IP  - 3
DP  - 2016 Jun
TI  - Distinct activation of primary human BDCA1(+) dendritic cells upon interaction 
      with stressed or infected beta cells.
PG  - 293-307
LID - 10.1111/cei.12779 [doi]
AB  - 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(+) 
      DCs towards differentially stressed pancreatic beta cells. Our data show that 
      BDCA1(+) DCs in human pancreas-draining lymph node (pdLN) suspensions and 
      blood-derived BDCA1(+) DCs both effectively engulf beta cells, thus mimicking 
      physiological conditions. Upon uptake of enterovirus-infected, but not 
      mock-infected cells, BDCA1(+) DCs induced interferon (IFN)-alpha/beta responses, 
      co-stimulatory molecules and proinflammatory cytokines and chemokines. Notably, 
      induction of stress in beta 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 beta cells and required RNA within virally infected cells. DCs encountering 
      enterovirus-infected beta cells, but not those incubated with mock-infected or 
      stressed beta cells, suppressed T helper type 2 (Th2) cytokines and variably induced 
      IFN-gamma in allogeneic mixed lymphocyte reaction (MLR). Thus, stressed beta cells have 
      little effect on human BDCA1(+) DC activation and function, while 
      enterovirus-infected beta cells impact these cells significantly, which could help 
      to explain their role in development of autoimmune diabetes in individuals at 
      risk.
CI  - (c) 2016 British Society for Immunology.
FAU - Schulte, B M
AU  - Schulte BM
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, the Netherlands.
FAU - Kers-Rebel, E D
AU  - Kers-Rebel ED
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, the Netherlands.
FAU - Bottino, R
AU  - Bottino R
AD  - Department of Pediatrics, Diabetes Institute, University of Pittsburgh, 
      Pittsburgh, PA, USA.
FAU - Piganelli, J D
AU  - Piganelli JD
AD  - Department of Pediatrics, Diabetes Institute, University of Pittsburgh, 
      Pittsburgh, PA, USA.
FAU - Galama, J M D
AU  - Galama JM
AD  - Department of Medical Microbiology, Radboud University Medical Center, Nijmegen.
FAU - Engelse, M A
AU  - Engelse MA
AD  - Department of Nephrology, Leiden University Medical Center, Leiden.
FAU - de Koning, E J P
AU  - de Koning EJ
AD  - Department of Nephrology, Leiden University Medical Center, Leiden.
AD  - Department of Endocrinology, Leiden University Medical Center, Leiden.
AD  - Hubrecht Institute, Utrecht, the Netherlands.
FAU - Adema, G J
AU  - Adema GJ
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, the Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160323
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Antigens, CD1)
RN  - 0 (CD1C protein, human)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Glycoproteins)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Antigens, CD1/genetics/*immunology
MH  - Cell Communication/*immunology
MH  - Coculture Techniques
MH  - Culture Media, Serum-Free/pharmacology
MH  - Dendritic Cells/cytology/drug effects/*immunology
MH  - Enterovirus B, Human/*immunology/pathogenicity
MH  - Gene Expression
MH  - Glycoproteins/genetics/*immunology
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Insulin-Secreting Cells/drug effects/*immunology/pathology/virology
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-1beta/pharmacology
MH  - Mice
MH  - Phagocytosis/drug effects
MH  - Poly I-C/pharmacology
MH  - Primary Cell Culture
MH  - Signal Transduction
MH  - Stress, Physiological
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Ultraviolet Rays
PMC - PMC4872385
OTO - NOTNLM
OT  - BDCA1+ myeloid DC
OT  - DC maturation
OT  - enterovirus
OT  - human
OT  - islets of Langerhans
OT  - beta cells
EDAT- 2016/02/19 06:00
MHDA- 2017/03/23 06:00
PMCR- 2017/06/01
CRDT- 2016/02/19 06:00
PHST- 2016/02/14 00:00 [accepted]
PHST- 2016/02/19 06:00 [entrez]
PHST- 2016/02/19 06:00 [pubmed]
PHST- 2017/03/23 06:00 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - CEI12779 [pii]
AID - 10.1111/cei.12779 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2016 Jun;184(3):293-307. doi: 10.1111/cei.12779. Epub 2016 Mar 
      23.