PMID- 28865147
OWN - NLM
STAT- MEDLINE
DCOM- 20180619
LR  - 20180620
IS  - 1365-2222 (Electronic)
IS  - 0954-7894 (Linking)
VI  - 47
IP  - 11
DP  - 2017 Nov
TI  - Differential regulation of PD-1 and its ligands in allergic asthma.
PG  - 1417-1425
LID - 10.1111/cea.13017 [doi]
AB  - BACKGROUND: Targeting PD-1/PD-1 ligand signalling is an established treatment 
      option for cancer. The role of these molecules in allergic asthma has been 
      investigated in several mouse studies yielding conflicting results. However, 
      human studies investigating the expression and regulation of PD-1 and its ligands 
      in allergic inflammation are lacking. OBJECTIVE: To analyse the expression and 
      regulation of PD-1 and its ligands in human allergic asthma. METHODS: The 
      well-established human asthma model of segmental allergen challenge (SAC) was 
      used to analyse the regulation of PD-1 and its ligands PD-L1 and PD-L2 on T 
      lymphocytes and dendritic cells by flow cytometry. The impact of immunoglobulin E 
      (IgE)-mediated signalling on PD-L1 expression was analysed on isolated 
      plasmacytoid dendritic cells (pDCs). RESULTS: PD-1 expression by blood CD4(+) T 
      cells was negatively associated with total and specific (against the allergen 
      used for provocation) IgE serum concentrations. Twenty-four hours after SAC, a 
      small decrease in endobronchial PD-1(+) CD4(+) T cells was accompanied by an 
      increase in PD-L1 expression on endobronchial myeloid dendritic cells (mDCs) and 
      pDCs. The PD-L1 up-regulation on pDCs was not induced by IgE-mediated mechanisms. 
      In contrast, PD-L2 was only detected on endobronchial mDCs and was significantly 
      down-regulated 24 hours after SAC. CONCLUSION AND CLINICAL RELEVANCE: This study 
      shows, for the first time, an association of a low PD-1 expression by circulating 
      CD4(+) T cells with high total and specific (against the allergen used for 
      provocation) IgE concentrations in allergic asthma. In addition, we demonstrate a 
      differential regulation of PD-1 ligands on endobronchial DCs after allergen 
      challenge which may favour Th2 inflammation. Therefore, modulating PD-1 
      ligand-mediated pathways might be a promising target in allergic asthma.
CI  - (c) 2017 John Wiley & Sons Ltd.
FAU - Bratke, K
AU  - Bratke K
AUID- ORCID: 0000-0001-6859-3736
AD  - Department of Pneumology, University of Rostock, Rostock, Germany.
FAU - Fritz, L
AU  - Fritz L
AD  - Department of Pneumology, University of Rostock, Rostock, Germany.
FAU - Nokodian, F
AU  - Nokodian F
AD  - Department of Pneumology, University of Rostock, Rostock, Germany.
FAU - Geissler, K
AU  - Geissler K
AD  - Department of Pneumology, University of Rostock, Rostock, Germany.
FAU - Garbe, K
AU  - Garbe K
AD  - Department of Pneumology, University of Rostock, Rostock, Germany.
FAU - Lommatzsch, M
AU  - Lommatzsch M
AD  - Department of Pneumology, University of Rostock, Rostock, Germany.
FAU - Virchow, J C
AU  - Virchow JC
AD  - Department of Pneumology, University of Rostock, Rostock, Germany.
LA  - eng
PT  - Journal Article
DEP - 20171012
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Allergens)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (Ligands)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adult
MH  - Allergens/immunology
MH  - Asthma/diagnosis/drug therapy/*immunology/*metabolism
MH  - B7-H1 Antigen/metabolism
MH  - Bronchoalveolar Lavage Fluid/cytology/immunology
MH  - Dendritic Cells/immunology/metabolism
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Immunoglobulin E/immunology
MH  - *Immunomodulation
MH  - Ligands
MH  - Male
MH  - Middle Aged
MH  - Programmed Cell Death 1 Receptor/*metabolism
MH  - Receptors, IgE/metabolism
MH  - Respiratory Function Tests
MH  - Signal Transduction
MH  - T-Lymphocytes/immunology/metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - IgE
OT  - T cells
OT  - asthma
OT  - basic mechanisms
OT  - dendritic cells
EDAT- 2017/09/03 06:00
MHDA- 2018/06/21 06:00
CRDT- 2017/09/03 06:00
PHST- 2016/10/24 00:00 [received]
PHST- 2017/08/10 00:00 [revised]
PHST- 2017/08/23 00:00 [accepted]
PHST- 2017/09/03 06:00 [pubmed]
PHST- 2018/06/21 06:00 [medline]
PHST- 2017/09/03 06:00 [entrez]
AID - 10.1111/cea.13017 [doi]
PST - ppublish
SO  - Clin Exp Allergy. 2017 Nov;47(11):1417-1425. doi: 10.1111/cea.13017. Epub 2017 
      Oct 12.