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.
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.
Authors: Hiam Abdala-Valencia; Mackenzie E Coden; Sergio E Chiarella; Elizabeth A Jacobsen; Bruce S Bochner; James J Lee; Sergejs Berdnikovs Journal: J Leukoc Biol Date: 2018-04-14 Impact factor: 4.962
Authors: David W Morris; Emily M Stucke; Lisa J Martin; J Pablo Abonia; Vincent A Mukkada; Philip E Putnam; Marc E Rothenberg; Patricia C Fulkerson Journal: J Allergy Clin Immunol Date: 2016-05-16 Impact factor: 10.793
Authors: Kewal Asosingh; Amit Vasanji; Aaron Tipton; Kimberly Queisser; Nicholas Wanner; Allison Janocha; Deepa Grandon; Bela Anand-Apte; Marc E Rothenberg; Raed Dweik; Serpil C Erzurum Journal: J Immunol Date: 2016-01-25 Impact factor: 5.422
Authors: Laura K Johnston; Chia-Lin Hsu; Rebecca A Krier-Burris; Krishan D Chhiba; Karen B Chien; Andrew McKenzie; Sergejs Berdnikovs; Paul J Bryce Journal: J Immunol Date: 2016-09-28 Impact factor: 5.422