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Myeloid dendritic cells are primed in allergic asthma for thymic stromal lymphopoietin‐mediated induction of Th2 and Th9 responses
Author(s) -
Froidure A.,
Shen C.,
Gras D.,
Van Snick J.,
Chanez P.,
Pilette C.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12435
Subject(s) - thymic stromal lymphopoietin , immunology , medicine , allergic inflammation , myeloid , asthma
Background Type 1 myeloid dendritic cells ( mDC s) contribute to inception of allergic asthma ( AA ) and are regulated by epithelial‐derived cytokines. Objectives To evaluate whether mDC s from AA patients are primed for thymic stromal lymphopoietin ( TSLP )‐driven responses. Methods mDC s from 18 AA patients and 15 controls were purified using immunomagnetic sorting. Cells were pulsed with TSLP or Dermatophagoides pteronyssinus (Der p) allergen, before FACS phenotyping and co‐culture with allogeneic CD4 + T cells. Bronchial biopsies from 15 AA patients and four controls were immunostained for CD 1c and TSLP receptor ( TSLPR ). Results Allergic asthma patients had a higher proportion of TSLPR + m DC s, in blood and bronchial mucosa. When compared to m DC s from controls, both TSLP ‐ and Der p‐pulsed blood mDC s from AA patients induced increased polarization of CD 4 + T cells into Th2 cells ( IL ‐5, IL ‐13, and GATA3 + ), while only TSLP ‐ mDC s promoted Th9 cells (IL‐9 and PU.1 + /IRF4 + ). In addition, OX40L was induced upon TSLP stimulation and was required for the induction of Th2, but not Th9, cells. In contrast, development of Th9 cells in this model depended on TGF ‐β1. Conclusions Our data indicate overlapping but partially distinct effects of TSLP and Der p allergen pathways, showing that DC s are primed in human asthma for TSLP ‐driven induction of both Th2 and Th9 cells. This novel TSLP / mDC /Th9 axis operates through a distinct, OX40L‐independent pathway. These data further highlight the TSLP pathway as a relevant target in human asthma.