Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control.
The hallmark of atopic asthma is transient airways hyperresponsiveness (AHR) preceded by aeroallergen-induced Th-cell activation. This is preceded by upregulation of CD86 on resident airway dendritic cells (DCs) that normally lack competence in T-cell triggering. Moreover, AHR duration is controlled via T-regulatory (Treg) cells, which can attenuate CD86 upregulation on DC. We show that airway mucosal Treg/DC interaction represents an accessible therapeutic target for asthma control. Notably, baseline airway Treg activity in sensitized rats can be boosted by microbe-derived stimulation of the gut, resulting in enhanced capacity to control CD86 expression on airway DC triggered by aeroallergen and accelerated resolution of AHR.
Strickland
D H
DH
Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
Judd
S
S
Thomas
J A
JA
Larcombe
A N
AN
Sly
P D
PD
Holt
P G
PG
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000382:microbiology / Q000628:therapy*; D051940:B7-2 Antigen / Q000235:genetics; D001419:Bacteria / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002457:Cell Extracts / Q000276:immunology* / Q000627:therapeutic use; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051381:Rats; D012137:Respiratory System / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000095983:Bacterial Lysates
D051940:B7-2 Antigen; D002457:Cell Extracts; D016207:Cytokines; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates; C500522:Foxp3 protein, rat