Jia Song1, Hai Wang1, Ya-Na Zhang2, Ping-Ping Cao1, Bo Liao1, Zhe-Zheng Wang1, Li-Li Shi1, Yin Yao1, Guan-Ting Zhai1, Zhi-Chao Wang1, Li-Meng Liu3, Ming Zeng1, Xiang Lu1, Heng Wang1, Xiang-Ping Yang4, Di Yu5, Claus Bachert6, Zheng Liu7. 1. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Otolaryngology-Head and Neck Surgery, Guangzhou Women and Children's Medical Center, Guangzhou, China. 3. No.1 Middle School affiliated to Central China Normal University, Wuhan, China. 4. Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 5. Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia. 6. Upper Airways Research Laboratory, Ghent University, Ghent, Belgium. 7. 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 contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. OBJECTIVE: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. METHODS: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. RESULTS: Increased formation of eLTs with germinal center-like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. CONCLUSION: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.
BACKGROUND: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. OBJECTIVE: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. METHODS: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. RESULTS: Increased formation of eLTs with germinal center-like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. CONCLUSION: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.
Authors: Jonas Eckrich; Julia Hinkel; Anna Fischl; Eva Herrmann; Gabriele Holtappels; Claus Bachert; Stefan Zielen Journal: World Allergy Organ J Date: 2020-06-23 Impact factor: 4.084
Authors: Ya Na Zhang; Jia Song; Guan Ting Zhai; Hai Wang; Ren Zhong Luo; Jing Xian Li; Bo Liao; Jin Ma; Heng Wang; Xiang Lu; Da Bo Liu; Zheng Liu Journal: Allergy Asthma Immunol Res Date: 2020-03 Impact factor: 5.764
Authors: Karim Boustani; Poonam Ghai; Rachele Invernizzi; Richard J Hewitt; Toby M Maher; Quan-Zhen Li; Philip L Molyneaux; James A Harker Journal: ERJ Open Res Date: 2022-02-14