Myeloid dendritic cells are primed in allergic asthma for thymic stromal lymphopoietin‐mediated induction of Th2 and Th9 responses. Issue 8 (3rd June 2014)

• Record Type: Journal Article
• Authors: Froidure, A.; Shen, C.; Gras, D.; Van Snick, J.; Chanez, P.; Pilette, C.
• Is Part Of: Allergy. Volume 69:Issue 8(2014:Aug.)
• Page Start: 1068
• Page End: 1076
• Publication Date: 2014-06-03
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12435
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12435-abs-0001"> <title>Abstract</title> <sec id="all12435-sec-0001" sec-type="section"> <title>Background</title> <p>Type 1 myeloid dendritic cells (mDCs) contribute to inception of allergic asthma (AA) and are regulated by epithelial‐derived cytokines.</p> </sec> <sec id="all12435-sec-0002" sec-type="section"> <title>Objectives</title> <p>To evaluate whether mDCs from AA patients are primed for thymic stromal lymphopoietin (TSLP)‐driven responses.</p> </sec> <sec id="all12435-sec-0003" sec-type="section"> <title>Methods</title> <p>mDCs from 18 AA patients and 15 controls were purified using immunomagnetic sorting. Cells were pulsed with TSLP or <italic>Dermatophagoides pteronyssinus</italic> (Der p) allergen, before FACS phenotyping and co‐culture with allogeneic CD4<sup>+</sup> T cells. Bronchial biopsies from 15 AA patients and four controls were immunostained for CD1c and TSLP receptor (TSLPR).</p> </sec> <sec id="all12435-sec-0004" sec-type="section"> <title>Results</title> <p>Allergic asthma patients had a higher proportion of TSLPR<sup>+</sup> mDCs, in blood and bronchial mucosa. When compared to mDCs from controls, both TSLP‐ and Der p‐pulsed blood mDCs from AA patients induced increased polarization of CD4<sup>+</sup> T cells into Th2 cells (IL‐5, IL‐13, and GATA3<sup>+</sup>), while only TSLP‐mDCs promoted Th9 cells (IL‐9 and PU.1<sup>+</sup>/IRF4<sup>+</sup>). 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.</p> </sec> <sec id="all12435-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Our data indicate overlapping but partially distinct effects of TSLP and Der p allergen pathways, showing that DCs 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.</p> </sec> </abstract>