PMID- 25860995
OWN - NLM
STAT- MEDLINE
DCOM- 20160331
LR  - 20190223
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Immunosuppression in early postnatal days induces persistent and 
      allergen-specific immune tolerance to asthma in adult mice.
PG  - e0122990
LID - 10.1371/journal.pone.0122990 [doi]
LID - e0122990
AB  - Bronchial asthma is a chronic airway inflammatory condition with high morbidity, 
      and effective treatments for asthma are limited. Allergen-specific immunotherapy 
      can only induce peripheral immune tolerance and is not sustainable. Exploring new 
      therapeutic strategies is of great clinical importance. Recombinant adenovirus 
      (rAdV) was used as a vector to make cells expressing cytotoxic T 
      lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 
      immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the 
      rAdVs together with allergens. Then these modified DCs were transplanted to mice 
      before allergen sensitization. The persistence and specificity of immune 
      tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 
      months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 
      secretion, and T cell stimulation in vitro. Mice treated with these DCs in the 
      early neonatal period developed tolerance against the allergens that were used to 
      induce asthma in the adult stage. Asthma symptoms, lung damage, airway 
      reactivity, and inflammatory response all improved. Humoral immunity indices 
      showed that this therapeutic strategy strongly suppressed mice immune responses 
      and was maintained for as long as 7 months. Furthermore, allergen 
      cross-sensitization and challenge experiments demonstrated that this immune 
      tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early 
      neonatal period, inducing persistent and allergen-specific immune tolerance to 
      asthma in adult mice. Our results suggest that it may be possible to develop a 
      vaccine for asthma.
FAU - Chen, Yan
AU  - Chen Y
AD  - Department of Respiratory Medicine, Children's Hospital of Fudan University, 
      Shanghai, China.
FAU - Zhang, Jin
AU  - Zhang J
AD  - Department of Respiratory Medicine, Children's Hospital of Fudan University, 
      Shanghai, China.
FAU - Lu, Yong
AU  - Lu Y
AD  - Department of Respiratory Medicine, Children's Hospital of Fudan University, 
      Shanghai, China.
FAU - Wang, Libo
AU  - Wang L
AD  - Department of Respiratory Medicine, Children's Hospital of Fudan University, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150410
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Allergens)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Allergens/*immunology
MH  - Animals
MH  - Animals, Newborn
MH  - Asthma/immunology/metabolism/*pathology
MH  - Bone Marrow Cells/cytology
MH  - CTLA-4 Antigen/genetics
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/immunology/metabolism
MH  - Desensitization, Immunologic
MH  - Genetic Vectors/genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - *Immune Tolerance
MH  - Immunity, Humoral
MH  - Immunoglobulin E/blood
MH  - Interleukin-10/blood/metabolism
MH  - Interleukin-12/blood/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Ovalbumin/immunology
MH  - Recombinant Fusion Proteins/biosynthesis/genetics
PMC - PMC4393286
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/04/11 06:00
MHDA- 2016/04/01 06:00
PMCR- 2015/04/10
CRDT- 2015/04/11 06:00
PHST- 2014/07/19 00:00 [received]
PHST- 2015/02/26 00:00 [accepted]
PHST- 2015/04/11 06:00 [entrez]
PHST- 2015/04/11 06:00 [pubmed]
PHST- 2016/04/01 06:00 [medline]
PHST- 2015/04/10 00:00 [pmc-release]
AID - PONE-D-14-32363 [pii]
AID - 10.1371/journal.pone.0122990 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 10;10(4):e0122990. doi: 10.1371/journal.pone.0122990. 
      eCollection 2015.