PMID- 25243789
OWN - NLM
STAT- MEDLINE
DCOM- 20150324
LR  - 20211021
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 135
IP  - 2
DP  - 2015 Feb
TI  - Dissolving microneedle delivery of nanoparticle-encapsulated antigen elicits 
      efficient cross-priming and Th1 immune responses by murine Langerhans cells.
PG  - 425-434
LID - S0022-202X(15)37099-8 [pii]
LID - 10.1038/jid.2014.415 [doi]
AB  - Dendritic cells (DCs) of the skin have an important role in skin-mediated 
      immunity capable of promoting potent immune responses. We availed of polymeric 
      dissolving microneedle (MN) arrays laden with nano-encapsulated antigen to 
      specifically target skin DC networks. This modality of immunization represents an 
      economic, efficient, and potent means of antigen delivery directly to skin DCs, 
      which are inefficiently targeted by more conventional immunization routes. 
      Following MN immunization, Langerhans cells (LCs) constituted the major skin DC 
      subset capable of cross-priming antigen-specific CD8+ T cells ex vivo. Although 
      all DC subsets were equally efficient in priming CD4+ T cells, LCs were largely 
      responsible for orchestrating the differentiation of CD4+ IFN-gamma- and 
      IL-17-producing effectors. Importantly, depletion of LCs prior to immunization 
      had a profound effect on CD8+ CTL responses in vivo, and vaccinated animals 
      displayed reduced protective anti-tumor and viral immunity. Interestingly, this 
      cross-priming bias was lost following MN immunization with soluble antigen, 
      suggesting that processing and cross-presentation of nano-particulate antigen is 
      favored by LCs. Therefore, these studies highlight the importance of LCs in skin 
      immunization strategies and that targeting of nano-particulate immunogens through 
      dissolvable polymeric MNs potentially provides a promising technological platform 
      for improved vaccination strategies.
FAU - Zaric, Marija
AU  - Zaric M
AD  - The Centre for Infection and Immunity, School of Medicine, Dentistry and 
      Biomedical Sciences, Queen's University Belfast, Belfast, UK.
FAU - Lyubomska, Oksana
AU  - Lyubomska O
AD  - The Centre for Infection and Immunity, School of Medicine, Dentistry and 
      Biomedical Sciences, Queen's University Belfast, Belfast, UK.
FAU - Poux, Candice
AU  - Poux C
AD  - The Centre for Infection and Immunity, School of Medicine, Dentistry and 
      Biomedical Sciences, Queen's University Belfast, Belfast, UK.
FAU - Hanna, Mary L
AU  - Hanna ML
AD  - The Centre for Infection and Immunity, School of Medicine, Dentistry and 
      Biomedical Sciences, Queen's University Belfast, Belfast, UK.
FAU - McCrudden, Maeliosa T
AU  - McCrudden MT
AD  - School of Pharmacy, Queen's University Belfast, Belfast, UK.
FAU - Malissen, Bernard
AU  - Malissen B
AD  - Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Universite, 
      Marseille, France; INSERM U1104, Marseille, France; CNRS UMR7280, Marseille, 
      France.
FAU - Ingram, Rebecca J
AU  - Ingram RJ
AD  - The Centre for Infection and Immunity, School of Medicine, Dentistry and 
      Biomedical Sciences, Queen's University Belfast, Belfast, UK.
FAU - Power, Ultan F
AU  - Power UF
AD  - The Centre for Infection and Immunity, School of Medicine, Dentistry and 
      Biomedical Sciences, Queen's University Belfast, Belfast, UK.
FAU - Scott, Christopher J
AU  - Scott CJ
AD  - School of Pharmacy, Queen's University Belfast, Belfast, UK.
FAU - Donnelly, Ryan F
AU  - Donnelly RF
AD  - School of Pharmacy, Queen's University Belfast, Belfast, UK.
FAU - Kissenpfennig, Adrien
AU  - Kissenpfennig A
AD  - The Centre for Infection and Immunity, School of Medicine, Dentistry and 
      Biomedical Sciences, Queen's University Belfast, Belfast, UK. Electronic address: 
      a.kissenpfennig@qub.ac.uk.
LA  - eng
GR  - BB/E020534/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/FOF/287/Biotechnology and Biological Sciences Research Council/United Kingdom
GR  - WT088532MA/Wellcome Trust/United Kingdom
GR  - WT094085MA/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140922
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Antigens)
RN  - 0 (Antigens, Surface)
RN  - 0 (Cd207 protein, mouse)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose-Binding Lectins)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Antigens/*administration & dosage
MH  - Antigens, Surface/analysis
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cross-Priming/*immunology
MH  - Immunization
MH  - Langerhans Cells/*immunology
MH  - Lectins, C-Type/analysis
MH  - Mannose-Binding Lectins/analysis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nanoparticles
MH  - Ovalbumin/immunology
MH  - Sendai virus/immunology
MH  - Th1 Cells/*immunology
MH  - Th17 Cells/immunology
EDAT- 2014/09/23 06:00
MHDA- 2015/03/25 06:00
CRDT- 2014/09/23 06:00
PHST- 2014/04/07 00:00 [received]
PHST- 2014/07/17 00:00 [revised]
PHST- 2014/08/26 00:00 [accepted]
PHST- 2014/09/23 06:00 [entrez]
PHST- 2014/09/23 06:00 [pubmed]
PHST- 2015/03/25 06:00 [medline]
AID - S0022-202X(15)37099-8 [pii]
AID - 10.1038/jid.2014.415 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2015 Feb;135(2):425-434. doi: 10.1038/jid.2014.415. Epub 2014 
      Sep 22.