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J Allergy Clin Immunol. 2015 Jun;135(6):1594-602. doi: 10.1016/j.jaci.2014.12.1918. Epub 2015 Feb 3.

Thymic stromal lymphopoietin and IL-33 modulate migration of hematopoietic progenitor cells in patients with allergic asthma.

Author information

1
Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario, Canada.
2
Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
3
Inflammation Research, Amgen, Seattle, Wash.
4
Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario, Canada. Electronic address: sehmir@mcmaster.ca.

Abstract

BACKGROUND:

Thymic stromal lymphopoietin (TSLP) and IL-33 are considered important initiators of type 2 immunity. In asthmatic patients allergic inflammatory responses are associated with increased lung homing of bone marrow-derived CD34(+) hematopoietic progenitor cells (HPCs), which include eosinophil lineage-committed progenitor cells. In this study we investigated the role of TSLP and IL-33 in the recruitment of progenitor cells to the airways in asthmatic subjects.

OBJECTIVES:

We sought (i) to examine the effect of allergen inhalation challenge on expression levels of receptors for TSLP (thymic stromal lymphopoietin receptor [TSLPR] and CD127) and IL-33 (ST2) and (ii) investigate the functional effects of these cytokines on HPCs.

METHODS:

Consenting patients with mild atopic asthma (n = 19) with an FEV1 of 70% or greater and methacholine PC20 of 16 mg/mL or less were recruited. Blood- and sputum-extracted progenitors were phenotyped by flow cytometry before and 24 hours after allergen challenge. Functional responses, including cytokine production and migration to TSLP and IL-33, were assessed in vitro.

RESULTS:

Significant increases in mature eosinophil, HPC, and eosinophil lineage-committed progenitor cell counts in sputum were observed 24 hours after allergen and were associated with a significant allergen-induced increase in HPCs expressing TSLPR, CD127, and ST2. Pre-exposure to TSLP and IL-33 primed the migration of HPCs to a potent progenitor cell chemoattractant, stromal cell-derived factor 1α (CXCL12). Incubation with TSLP and IL-33 stimulated significant production of IL-5 and IL-13, but not IL-4, by HPCs. This priming effect was inhibited by blocking antibodies to TSLPR and ST2, respectively, and IL-13 receptor α1 in both scenarios.

CONCLUSIONS:

In allergic asthmatic responses increased lung homing of HPCs may be orchestrated by TSLP and IL-33 through an IL-13-dependent axis.

KEYWORDS:

Hematopoietic progenitor cells; asthma; thymic stromal lymphopoietin

PMID:
25656998
DOI:
10.1016/j.jaci.2014.12.1918
[Indexed for MEDLINE]

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