Ya-Na Zhang1, Jia Song2, Hai Wang2, Heng Wang2, Ming Zeng2, Guan-Ting Zhai2, Jin Ma2, Zhi-Yong Li2, Bo Liao2, Bao-Feng Wang2, Zhen Zhen3, Nan Wang2, Ping-Ping Cao2, Peng Lin4, Qin Ning5, Zheng Liu6. 1. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Otolaryngology-Head and Neck Surgery, Tianjin First Center Hospital, Tianjin, China. 2. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 3. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Otolaryngology-Head and Neck Surgery, Peking University First Hospital, Beijing, China. 4. Department of Otolaryngology-Head and Neck Surgery, Tianjin First Center Hospital, Tianjin, China. 5. Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 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: Locally produced IgE contributes to the initiation and development of eosinophilic inflammation in eosinophilic nasal polyps independent of systemic atopy. However, whether CXCR5(+)CD4(+) T follicular helper (TFH) cells are involved in local IgE production at mucosal sites remains unexplored. OBJECTIVE: We sought to explore the presence, phenotype, and function of CXCR5(+)CD4(+) TFH cells in eosinophilic nasal polyp tissues compared with noneosinophilic nasal polyp and control normal nasal tissues. METHODS: TFH cell-surface phenotypes and subsets and B-cell subsets in nasal tissues and peripheral blood were studied by means of flow cytometry. Immunohistochemistry was used to detect the tissue location of TFH cells. Sorted nasal TFH cells and CXCR5(-) T cells were cultured with autologous naive B cells purified from blood. RESULTS: Nasal TFH cells expressed inducible costimulator, programmed cell death protein 1, and the transcription factor B-cell lymphoma 6 (Bcl-6) at an intermediate level when compared with bona fide TFH cells in tonsils and circulating TFH cells. Although counts of total TFH cells and IL-21(+), IFN-γ(+), and IL-17(+) TFH cells were increased in both eosinophilic and noneosinophilic nasal polyp tissues compared with those in normal nasal tissues, IL-4(+) TFH cell counts were only increased in eosinophilic polyp tissues. IL-4 and IL-21 were involved in polyp TFH cell-induced IgE production from naive B cells, and nasal IL-4(+) TFH cell counts correlated highly with local IgE levels in vivo. IL-4(+)Bcl-6(+)CD4(+) TFH cells were identified in ectopic lymphoid structures in eosinophilic nasal polyps. TFH cells also positively correlated with germinal center B cells and plasma cells in nasal tissues. CONCLUSION: Nasal IL-4(+) TFH cells might be involved in local IgE production in eosinophilic nasal polyps.
BACKGROUND: Locally produced IgE contributes to the initiation and development of eosinophilic inflammation in eosinophilic nasal polyps independent of systemic atopy. However, whether CXCR5(+)CD4(+) T follicular helper (TFH) cells are involved in local IgE production at mucosal sites remains unexplored. OBJECTIVE: We sought to explore the presence, phenotype, and function of CXCR5(+)CD4(+) TFH cells in eosinophilic nasal polyp tissues compared with noneosinophilic nasal polyp and control normal nasal tissues. METHODS: TFH cell-surface phenotypes and subsets and B-cell subsets in nasal tissues and peripheral blood were studied by means of flow cytometry. Immunohistochemistry was used to detect the tissue location of TFH cells. Sorted nasal TFH cells and CXCR5(-) T cells were cultured with autologous naive B cells purified from blood. RESULTS: Nasal TFH cells expressed inducible costimulator, programmed cell death protein 1, and the transcription factor B-cell lymphoma 6 (Bcl-6) at an intermediate level when compared with bona fide TFH cells in tonsils and circulating TFH cells. Although counts of total TFH cells and IL-21(+), IFN-γ(+), and IL-17(+) TFH cells were increased in both eosinophilic and noneosinophilic nasal polyp tissues compared with those in normal nasal tissues, IL-4(+) TFH cell counts were only increased in eosinophilic polyp tissues. IL-4 and IL-21 were involved in polyp TFH cell-induced IgE production from naive B cells, and nasal IL-4(+) TFH cell counts correlated highly with local IgE levels in vivo. IL-4(+)Bcl-6(+)CD4(+) TFH cells were identified in ectopic lymphoid structures in eosinophilic nasal polyps. TFH cells also positively correlated with germinal center B cells and plasma cells in nasal tissues. CONCLUSION: Nasal IL-4(+) TFH cells might be involved in local IgE production in eosinophilic nasal polyps.
Authors: S Feldman; R Kasjanski; J Poposki; D Hernandez; J N Chen; J E Norton; L Suh; R G Carter; W W Stevens; A T Peters; R C Kern; D B Conley; B K Tan; S Shintani-Smith; K C Welch; L C Grammer; K E Harris; A Kato; R P Schleimer; K E Hulse Journal: Clin Exp Allergy Date: 2017-01-26 Impact factor: 5.018