TH1 signatures are present in the lower airways of children with severe asthma, regardless of allergic status

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:141

Article

Wisniewski, Julia A.^1,2  Muehling, Lyndsey M.¹  Eccles, Jacob D.¹  Capaldo, Brian J.³  Agrawal, Rachana¹  Shirley, Debbie-Ann²  Patrie, James T.⁴  Workman, Lisa J.¹  Schuyler, Alexander J.¹  Lawrence, Monica G.¹  Teague, W. Gerald²  Woodfolk, Judith A.¹ 

[1] Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA

[2] Univ Virginia, Sch Med, Dept Pediat, Charlottesville, VA 22908 USA

[3] Univ Virginia, Sch Med, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA

[4] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA

关键词: Severe asthma;    allergic;    IgE;    IFN-gamma;    IL-4;    IL-5;    IL-23;    IL-33;    IL-28A;    T(H)1 cells;    T(H)2 cells;    T(H)17 cells;    type 2 innate lymphoid cells;   

DOI  :  10.1016/j.jaci.2017.08.020

来源: Elsevier

【 摘 要 】

Background: The pathogenesis of severe asthma in childhood remains poorly understood. Objective: We sought to construct the immunologic landscape in the airways of children with severe asthma. Methods: Comprehensive analysis of multiple cell types and mediators was performed by using flow cytometry and a multiplex assay with bronchoalveolar lavage (BAL) specimens (n = 68) from 52 highly characterized allergic and nonallergic children (0.5-17 years) with severe treatment-refractory asthma. Multiple relationships were tested by using linear mixed-effects modeling. Results: Memory CCR5(+) T(H)1 cells were enriched in BAL fluid versus blood, and pathogenic respiratory viruses and bacteria were readily detected. IFN-gamma(+) IL-17(+) and IFN-gamma(-) 2 IL-17(+) subsets constituted secondary T-H types, and BAL fluid CD8 1 T cells were almost exclusively IFN-gamma(+). The T(H)17-associated mediators IL-23 and macrophage inflammatory protein 3 alpha/CCL20 were highly expressed. Despite low T(H)2 numbers, T(H)2 cytokines were detected, and T(H)2 skewing correlated with total IgE levels. Type 2 innate lymphoid cells and basophils were scarce in BAL fluid. Levels of IL-5, IL-33, and IL-28A/IFN-lambda 2 were increased in multisensitized children and correlated with IgE levels to dust mite, ryegrass, and fungi but not cat, ragweed, or food sources. Additionally, levels of IL-5, but no other cytokine, increased with age and correlated with eosinophil numbers in BAL fluid and blood. Both plasmacytoid and IgE 1 FceRI 1 myeloid dendritic cells were present in BAL fluid. Conclusions: The lower airways of children with severe asthma display a dominant T(H)1 signature and atypical cytokine profiles that link to allergic status. Our findings deviate from established paradigms and warrant further assessment of the pathogenicity of T(H)1 cells in patients with severe asthma.

【 授权许可】

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