Introduction: Nasal inverted papilloma (NIP) is a benign tumour with multiple inflammatory cell infiltration. Tertiary lymphoid organs (TLOs) support local antibody production and play important roles in airway inflammation. However, the evidence of TLOs and local immunoglobulins in NIP has not been reported yet. We investigated the presence of TLOs and immunoglobulins in NIP tissues and their association with the clinical-pathological characteristics of NIPs. Methods: We analyzed the occurrence and composition of TLOs and local immunoglobulins by immunohistochemistry and evaluated the lymph organogenesis associated genes and cytokines by quantitative qPCR and Luminex assays, respectively, in papilloma tissues from 84 NIP cases. Results: TLOs were present in 54% (45/84) of the NIP patients but not in control subjects. TLOs were composed of T cells, B cells, follicular dendritic cells, macrophages, and natural killer cells. Compared to NIP tissues without TLOs, tissues with TLOs showed significantly higher eosinophil infiltration levels (3.5-fold), elevation of lymphorganogenic genes (CXCL12, CXCL13, CCL20, CCL21, CD21L, and lymphotoxin alpha and beta), and increased Th17 (IL-21, IL-22, and GM-CSF) and Th2 (IL-5 and IL-13) cytokine production. Moreover, NIP with TLOs demonstrated a higher number of follicular T helper cells and immunoglobulin-producing plasma cells (CD138+ IgA+, CD138+ IgM+, CD138+ IgE+, and CD138+ IgG+) than those without TLOs, and these antibody-producing cells were positively correlated with the eosinophil number. Conclusion: The high frequency of TLOs and excess local immunoglobulin production are associated with an eosinophilic and Th2 skew microenvironment in the NIP mucosa, which would contribute to an important immunopathogenic response during NIP pathogenesis.
Int Arch Allergy Immunol

中文翻译：

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鼻内翻性乳头状瘤中三级淋巴器官的存在与嗜酸性粒细胞浸润和局部免疫球蛋白产生相关

简介：鼻内翻性乳头状瘤（NIP）是一种多发炎性细胞浸润的良性肿瘤。三级淋巴器官 (TLO) 支持局部抗体的产生，并在气道炎症中发挥重要作用。然而，尚未报道 NIP 中 TLO 和局部免疫球蛋白的证据。我们研究了 NIP 组织中 TLO 和免疫球蛋白的存在及其与 NIP 临床病理特征的关联。方法：我们通过免疫组织化学分析了 TLO 和局部免疫球蛋白的发生和组成，并分别通过定量 qPCR 和 Luminex 测定法评估了来自 84 例 NIP 病例的乳头状瘤组织中的淋巴器官发生相关基因和细胞因子。结果：TLO 存在于 54% (45/84) 的 NIP 患者中，但不存在于对照受试者中。TLO 由 T 细胞、B 细胞、滤泡树突细胞、巨噬细胞和自然杀伤细胞组成。与没有 TLOs 的 NIP 组织相比，有 TLOs 的组织显示出显着更高的嗜酸性粒细胞浸润水平（3.5 倍），淋巴器官基因（CXCL12、CXCL13、CCL20、CCL21、CD21L 和淋巴毒素 α 和β）升高，Th17（IL- 21、IL-22 和 GM-CSF）和 Th2（IL-5 和 IL-13）细胞因子的产生。此外，与没有 TLOs 的 NIP 相比，具有 TLOs 的 NIP 显示出更多数量的滤泡 T 辅助细胞和产生免疫球蛋白的浆细胞（CD138+ IgA+、CD138+ IgM+、CD138+ IgE+ 和 CD138+ IgG+），并且这些产生抗体的细胞与嗜酸性粒细胞数。结论：TLO 的高频率和过量的局部免疫球蛋白产生与 NIP 黏膜中的嗜酸性粒细胞和 Th2 偏斜微环境有关，这将有助于 NIP 发病过程中的重要免疫病理反应。
Int Arch 过敏免疫