PMID- 30817215
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20221215
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 5
DP  - 2019 May
TI  - Salivary gland immunization via Wharton's duct activates differential T-cell 
      responses within the salivary gland immune system.
PG  - 6011-6022
LID - 10.1096/fj.201801993R [doi]
AB  - Salivary glands are a major component of the mucosal immune system that confer 
      adaptive immunity to mucosal pathogens. As previously demonstrated, immunization 
      of the submandibular gland with tissue culture-derived murine cytomegalovirus 
      (tcMCMV) or replication-deficient adenoviruses expressing individual murine 
      cytomegalovirus (MCMV) genes protected mice against a lethal MCMV challenge. 
      Here, we report that salivary gland inoculation of BALB/cByJ mice with tcMCMV or 
      recombinant adenoviruses differentially activates T helper (T(h))1, -2, and -17 
      cells in the salivary glands vs. the associated lymph nodes. After inoculation 
      with tcMCMV, lymphocytes from the submandibular gland preferentially express the 
      transcription factor T-cell-specific T-box transcription factor (T-bet), which 
      controls the expression of the hallmark T(h)1 cytokine, IFN-gamma. Lymphocytes from 
      the periglandular lymph nodes (PGLNs) express both T-bet and GATA-binding protein 
      3 (GATA3), which promotes the secretion of IL-4, -5, and -10 from T(h)2 cells. In 
      contrast, after inoculation with replication-deficient adenoviruses, lymphocytes 
      from the submandibular gland express T-bet, GATA3, and RAR-related orphan 
      receptor gamma, thymus-specific isoform (RORgammat) (required for differentiation of 
      T(h)17 cells) and forkhead box P3 (Foxp3) (required for the differentiation of 
      regulatory T cells). Lymphocytes from the PGLNs were not activated. The 
      differential induction of T(h) responses in the salivary gland vs. the PGLNs 
      after inoculation with attenuated virus vs. a nominal protein antigen supports 
      the use of the salivary as an alternative mucosal route for administering 
      vaccines.-Liu, G., Zhang, F., Wang, R., London, S. D., London, L. Salivary gland 
      immunization via Wharton's duct activates differential T-cell responses within 
      the salivary gland immune system.
FAU - Liu, Guangliang
AU  - Liu G
AD  - Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook 
      University, Stony Brook, New York, USA.
FAU - Zhang, Fangfang
AU  - Zhang F
AD  - Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook 
      University, Stony Brook, New York, USA.
FAU - Wang, Ruixue
AU  - Wang R
AD  - Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook 
      University, Stony Brook, New York, USA.
FAU - London, Steven D
AU  - London SD
AD  - Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook 
      University, Stony Brook, New York, USA.
FAU - London, Lucille
AU  - London L
AD  - Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook 
      University, Stony Brook, New York, USA.
LA  - eng
GR  - R01 DE016652/DE/NIDCR NIH HHS/United States
GR  - R15 DE024313/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190228
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Cytokines)
RN  - 0 (GATA3 Transcription Factor)
RN  - 0 (Gata3 protein, mouse)
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (T-box transcription factor TBX21)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Cytokines/metabolism
MH  - Female
MH  - GATA3 Transcription Factor/metabolism
MH  - *Immunity, Mucosal
MH  - Interferon-gamma/metabolism
MH  - Lymph Nodes/pathology
MH  - Lymphocytes/cytology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Muromegalovirus
MH  - Salivary Ducts/*immunology
MH  - Salivary Glands/*immunology
MH  - T-Box Domain Proteins/metabolism
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - Vaccination
PMC - PMC6463922
OTO - NOTNLM
OT  - T helper cells
OT  - mucosal immunity
OT  - vaccine development
COIS- The authors thank Dr. John D. Shanley and Dr. Carol A. Wu (University of 
      Connecticut, Farmington, CT, USA) for providing recombinant adenovirus vectors 
      and cell lines. This project was supported by U.S. National Institutes of 
      Health/National Institute of Dental and Craniofacial Research Grant 1R01 DE016652 
      (to S.D.L.) and 1R15DE024313 (to S.D.L.). The authors declare no conflicts of 
      interest.
EDAT- 2019/03/01 06:00
MHDA- 2020/06/02 06:00
PMCR- 2020/02/28
CRDT- 2019/03/01 06:00
PHST- 2019/03/01 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2019/03/01 06:00 [entrez]
PHST- 2020/02/28 00:00 [pmc-release]
AID - FJ_201801993R [pii]
AID - 10.1096/fj.201801993R [doi]
PST - ppublish
SO  - FASEB J. 2019 May;33(5):6011-6022. doi: 10.1096/fj.201801993R. Epub 2019 Feb 28.