Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis

• Published in: The European respiratory journal Vol. 63; no. 5; p. 2400386
• Main Authors: Luo, Rong-Guang, Wu, Yi-Fan, Lu, Hai-Wen, Weng, Dong, Xu, Jia-Yan, Wang, Le-Le, Zhang, Li-Sha, Zhao, Cai-Qi, Li, Jian-Xiong, Yu, Yong, Jia, Xin-Ming, Xu, Jin-Fu
• Format: Journal Article
• Language: English
• Published: England European Respiratory Society 01.05.2024
• Subjects: Adult; Aspergillosis, Allergic Bronchopulmonary - immunology; Asthma - immunology; B-Lymphocytes - immunology; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Case-Control Studies; Female; Humans; Male; Middle Aged; Original s; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Th2 Cells - immunology
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/13993003.00386-2024

Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21 CD4 T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4 T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures were measured. ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5 IL-13 IL-21 CD4 T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5 IL-13 IL-21 CD4 T-cells were mainly peripheral T-helper (Tph) cells (PD-1 CXCR5 ), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5 IL-13 IL-21 Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured , Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE. We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.