Activated circulating T follicular helper cells and skewing of T follicular helper 2 cells are down-regulated by treatment including an inhaled corticosteroid in patients with allergic asthma

被引:18
作者
Miyajima, Satsuki [1 ]
Shigehara, Katsunori [2 ,4 ]
Kamekura, Ryuta [2 ,3 ]
Takaki, Hiromi [2 ]
Yabe, Hayato [1 ,2 ]
Ikegami, Ippei [2 ]
Asai, Yuichiro [1 ]
Nishikiori, Hirotaka [1 ]
Chiba, Hirohumi [1 ]
Uno, Eiji [4 ]
Takahashi, Hiroki [1 ]
Ichimiya, Shingo [2 ]
机构
[1] Sapporo Med Univ, Dept Resp Med & Allergol, Sch Med, Sapporo, Hokkaido, Japan
[2] Sapporo Med Univ, Res Inst Frontier Med, Dept Human Immunol, Sch Med, Sapporo, Hokkaido, Japan
[3] Sapporo Med Univ, Dept Otolaryngol, Sch Med, Sapporo, Hokkaido, Japan
[4] Ai Med Clin, Sapporo, Hokkaido, Japan
关键词
CXCL13; ICS; IgE; Regulatory B cell; T follicular helper cell; B-CELLS; IGE; PHENOTYPES; HUMANS; MUCOSA; CXCL13; ROLES;
D O I
10.1016/j.alit.2019.08.008
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: CXCR5(+) T follicular helper (T-FH) cells primarily promote B cells to produce an antigen-specific antibody through germinal centers (GCs). T-FH cells exist in circulation, and circulating(c) T(FH)2 cells, a subset of cT(FH) cells, are able to help naive B cells produce IgE in healthy individuals. Conversely, IL-10-producing regulatory B (Breg) cells inhibit an accelerated immune response. Methods: We investigated the roles of cT(FH) cells and cBreg cells based on a T(H)2 response in patients with atopic asthma (AA). Thirty-two patients with AA and 35 healthy volunteers (HV) were enrolled. We examined cT(FH) cells including their subsets, their expression of ICOS and PD-1, and cBreg cells by flow cytometry and their associations with clinical biomarkers. Plasma levels of CXCL13, which is a counterpart of CXCR5, were also measured using ELISA. Results: In patients with AA, cT(FH)2 cells were increased and cT(FH)1 cells were decreased compared with those in HV. The expression levels of ICOS on cT(FH) and their subset cells were elevated and Breg cells were greatly decreased. The plasma levels of CXCL13 in patients with AA were significantly elevated and correlated well with the cT(FH)2/cBreg ratio. These cells were examined in 10 patients AA before and after inhaled corticosteroid (ICS) treatment. Interestingly, the percentages and numbers of T(FH)2 and ICOS+ cT(FH) cells declined after ICS treatment together with improvements in symptoms and clinical biomarkers. Conclusions: The percentages and numbers of cT(FH)2 and ICOS+ cT(FH) cells might be useful as biomarkers of T(H)2 typed airway inflammation in patients with AA. Copyright (C) 2019, Japanese Society of Allergology. Production and hosting by Elsevier B.V.
引用
收藏
页码:66 / 77
页数:12
相关论文
共 43 条
  • [31] Regulatory B Cells: Origin, Phenotype, and Function
    Rosser, Elizabeth C.
    Mauri, Claudia
    [J]. IMMUNITY, 2015, 42 (04) : 607 - 612
  • [32] PD-1 Controls Follicular T Helper Cell Positioning and Function
    Shi, Jingwen
    Hou, Shiyue
    Fang, Qian
    Liu, Xin
    Liu, Xiaolong
    Qi, Hai
    [J]. IMMUNITY, 2018, 49 (02) : 264 - +
  • [33] Expansion of circulating follicular T helper cells associates with disease severity in childhood atopic dermatitis
    Szabo, Krisztina
    Gaspar, Krisztian
    Dajnoki, Zsolt
    Papp, Gabor
    Fabos, Beata
    Szegedi, Andrea
    Zeher, Margit
    [J]. IMMUNOLOGY LETTERS, 2017, 189 : 101 - 108
  • [34] Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma
    Takhar, Pooja
    Corrigan, Christopher J.
    Smurthwaite, Lyn
    O'Connor, Brian J.
    Durham, Stephen R.
    Lee, Tak H.
    Gould, Hannah J.
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 119 (01) : 213 - 218
  • [35] Pathophysiology of T follicular helper cells in humans and mice
    Ueno, Hideki
    Banchereau, Jacques
    Vinuesa, Carola G.
    [J]. NATURE IMMUNOLOGY, 2015, 16 (02) : 142 - 152
  • [36] Targeting the ICOS/ICOS-L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease
    Uwadiae, Faith I.
    Pyle, Chloe J.
    Walker, Simone A.
    Lloyd, Clare M.
    Harker, James A.
    [J]. ALLERGY, 2019, 74 (04) : 650 - 662
  • [37] CD24 hi CD27 + B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide
    van der Vlugt, L. E. P. M.
    Mlejnek, E.
    Ozir-Fazalalikhan, A.
    Bonas, M. Janssen
    Dijksman, T. R.
    Labuda, L. A.
    Schot, R.
    Guigas, B.
    Moller, G. M.
    Hiemstra, P. S.
    Yazdanbakhsh, M.
    Smits, H. H.
    [J]. CLINICAL AND EXPERIMENTAL ALLERGY, 2014, 44 (04) : 517 - 528
  • [38] Tfh1 Cells in Germinal Centers During Chronic HIV/SIV Infection
    Velu, Vijayakumar
    Mylvaganam, Geetha
    Ibegbu, Chris
    Amara, Rama Rao
    [J]. FRONTIERS IN IMMUNOLOGY, 2018, 9
  • [39] Follicular Helper T Cells
    Vinuesa, Carola G.
    Linterman, Michelle A.
    Yu, Di
    MacLennan, Ian C. M.
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, VOL 34, 2016, 34 : 335 - 368
  • [40] Asthma phenotypes: the evolution from clinical to molecular approaches
    Wenzel, Sally E.
    [J]. NATURE MEDICINE, 2012, 18 (05) : 716 - 725