Yin Yao1, Zhi-Chao Wang1, Nan Wang1, Peng-Cheng Zhou2, Cai-Ling Chen1, Jia Song1, Li Pan1, Bo Liao1, Xin-Hao Zhang1, Yong-Shi Yang3, Xiao-Yan Xu4, Rong-Fei Zhu3, Di Yu5, Zheng Liu6. 1. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia. 3. Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Department of Otolaryngology-Head and Neck Surgery, China Resources & Wisco General Hospital, Wuhan, China. 5. Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia. Electronic address: di.yu@anu.edu.au. 6. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhengliuent@hotmail.com.
Abstract
BACKGROUND: The function of follicular regulatory T (TFR) cells, especially in regulating IgE production in patients with allergic diseases, is poorly understood. OBJECTIVE: We sought to investigate the phenotype, function, and clinical relevance of TFR cells in patients with allergic rhinitis (AR). METHODS: The phenotype and frequency of tonsillar and circulating TFR cells were characterized by using flow cytometry. TFR cell function was examined in an assay by coculturing with follicular helper T cells and B cells. The associations between TFR cells and the clinical features in patients with AR before and after allergen immunotherapy (AIT) were analyzed. RESULTS: TFR cells were detected in germinal centers of tonsils, but compared with subjects without AR, the frequencies decreased in patients with AR who were allergic to house dust mites. Circulating TFR cells in blood were phenotypically and numerically correlated with tonsillar TFR cells, and a reduction of circulating TFR cells but not total or CXCR5- regulatory T cells was noted in patients with AR compared with healthy control subjects. Moreover, circulating TFR cells in patients with AR showed a specific defect in suppressing IgE production but were capable of suppressing production of other immunoglobulin types. We identified negative associations of circulating TFR cell frequencies and function with antigen-specific IgE levels or disease severity in patients with AR. After AIT, the frequencies and function of circulating TFR cells were improved, which positively associated with disease remission. CONCLUSION: Impairment in TFR cells might contribute to aberrant IgE production in patients with AR, and AIT improves defective TFR cell function. TFR cells might serve as a potential biomarker to monitor clinical response to AIT.
BACKGROUND: The function of follicular regulatory T (TFR) cells, especially in regulating IgE production in patients with allergic diseases, is poorly understood. OBJECTIVE: We sought to investigate the phenotype, function, and clinical relevance of TFR cells in patients with allergic rhinitis (AR). METHODS: The phenotype and frequency of tonsillar and circulating TFR cells were characterized by using flow cytometry. TFR cell function was examined in an assay by coculturing with follicular helper T cells and B cells. The associations between TFR cells and the clinical features in patients with AR before and after allergen immunotherapy (AIT) were analyzed. RESULTS:TFR cells were detected in germinal centers of tonsils, but compared with subjects without AR, the frequencies decreased in patients with AR who were allergic to house dust mites. Circulating TFR cells in blood were phenotypically and numerically correlated with tonsillar TFR cells, and a reduction of circulating TFR cells but not total or CXCR5- regulatory T cells was noted in patients with AR compared with healthy control subjects. Moreover, circulating TFR cells in patients with AR showed a specific defect in suppressing IgE production but were capable of suppressing production of other immunoglobulin types. We identified negative associations of circulating TFR cell frequencies and function with antigen-specific IgE levels or disease severity in patients with AR. After AIT, the frequencies and function of circulating TFR cells were improved, which positively associated with disease remission. CONCLUSION: Impairment in TFR cells might contribute to aberrant IgE production in patients with AR, and AIT improves defective TFR cell function. TFR cells might serve as a potential biomarker to monitor clinical response to AIT.
Authors: Markus M Xie; Qiang Chen; Hong Liu; Kai Yang; Byunghee Koh; Hao Wu; Soheila J Maleki; Barry K Hurlburt; Joan Cook-Mills; Mark H Kaplan; Alexander L Dent Journal: J Clin Invest Date: 2020-07-01 Impact factor: 14.808
Authors: Mostafa T Mohammed; Songjie Cai; Benjamin L Hanson; Hengcheng Zhang; Rachel L Clement; Joe Daccache; Cecilia B Cavazzoni; Bruce R Blazar; Alessandro Alessandrini; Helmut G Rennke; Anil Chandraker; Peter T Sage Journal: Am J Transplant Date: 2021-02-11 Impact factor: 9.369