Lopes Rafael S, Carvalho Pedro P, Pires Maria A, Rodrigues-Santos Paulo, Costa Eduardo, Requicha João F
Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro (UTAD), Vila Real, Portugal.
Vasco da Gama Research Center (CIVG), University School Vasco da Gama (EUVG), Campus Universitário de Lordemão, Coimbra, Portugal.
Front Immunol. 2025 Sep 11;16:1572631. doi: 10.3389/fimmu.2025.1572631. eCollection 2025.
A comprehensive understanding of the oral immune response in feline chronic gingivostomatitis (FCGS) is crucial for veterinarians to improve clinical and therapeutic decisions. This critical review addresses the local and systemic immune responses associated with FCGS.
A comprehensive database search was conducted using the PubMed/MEDLINE database, resulting in 3,358 studies. Following a rigorous screening process, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 17 publications were included in this review.
The local immune response in FCGS is primarily evaluated through histopathological and immunohistochemical analyses of oral biopsy samples, and by analysis of saliva. Histopathological analysis reveals a dense lymphoplasmacytic infiltration within the mucosa, indicating chronic inflammation. Immunohistochemical staining identifies increased numbers of mast cells, altered expression of immunoglobulins (IgG, IgM, and IgA) and presence of immunomarkers (CD3+, CD4+, CD8+ T cells and Mott cells), indicating immune dysregulation. Systemic immune features of FCGS are investigated in blood samples through flow cytometry, polymerase chain reaction, and enzyme-linked immunosorbent assay. A consistent finding is an increased level of pro-inflammatory cytokines (IL-6, TNF-α, and IFN-γ), indicating intense systemic immune activation. Neutrophilia, disrupted CD4/CD8 T-cell ratio, a reduction in CD21+ B cells and alterations in regulatory T cells expressing FOXP3, suggests chronic immune regulation dysfunction.
The findings highlight a complex relationship between local and systemic immune responses, by significant alterations in T cell subsets, pro-inflammatory cytokines, and immunoglobulin expression. The frequent presence of CD3+, CD4+, and CD8+ T cells, along with impaired regulatory T cell (FOXP3+) function, suggests that dysregulated cell-mediated immunity is a key factor in the pathogenesis of FCGS. Elevated systemic immunomarkers (IL-6, TNF-α, and IFN-γ), provide further evidence of a chronic immune activation state. The immunopathological similarities observed between FCGS and human oral lichen planus reinforce the potential of FCGS individuals as a spontaneous model for comparative research. This review found that there is a lack of comprehensive information on the oral immune response of FCGS. Further observational and experimental studies focusing on the link between local and systemic immune responses are essential to fully understand the complexity and guide the development of novel, evidence-based therapeutic strategies.
全面了解猫慢性龈口炎（FCGS）中的口腔免疫反应对于兽医改善临床和治疗决策至关重要。这篇批判性综述探讨了与FCGS相关的局部和全身免疫反应。
使用PubMed/MEDLINE数据库进行了全面的数据库检索，共检索到3358项研究。按照系统评价和Meta分析的首选报告项目（PRISMA）指南进行严格筛选后，本综述纳入了17篇出版物。
FCGS中的局部免疫反应主要通过对口腔活检样本进行组织病理学和免疫组织化学分析以及对唾液进行分析来评估。组织病理学分析显示黏膜内有密集的淋巴细胞和浆细胞浸润，表明存在慢性炎症。免疫组织化学染色可识别肥大细胞数量增加、免疫球蛋白（IgG、IgM和IgA）表达改变以及免疫标志物（CD3+、CD4+、CD8+ T细胞和莫特细胞）的存在，表明免疫失调。通过流式细胞术、聚合酶链反应和酶联免疫吸附测定对血液样本中的FCGS全身免疫特征进行研究。一个一致的发现是促炎细胞因子（IL-6、TNF-α和IFN-γ）水平升高，表明全身免疫强烈激活。中性粒细胞增多、CD4/CD8 T细胞比值紊乱、CD21+ B细胞减少以及表达FOXP3的调节性T细胞改变，提示慢性免疫调节功能障碍。
研究结果突出了局部和全身免疫反应之间的复杂关系，表现为T细胞亚群、促炎细胞因子和免疫球蛋白表达的显著改变。CD3+、CD4+和CD8+ T细胞的频繁存在以及调节性T细胞（FOXP3+）功能受损表明，细胞介导的免疫失调是FCGS发病机制中的一个关键因素。全身免疫标志物（IL-6、TNF-α和IFN-γ）升高进一步证明了慢性免疫激活状态。FCGS与人类口腔扁平苔藓之间观察到的免疫病理学相似性增强了FCGS个体作为比较研究自发模型的潜力。本综述发现，关于FCGS口腔免疫反应缺乏全面信息。进一步聚焦局部和全身免疫反应之间联系的观察性和实验性研究对于充分理解其复杂性并指导基于证据的新型治疗策略的开发至关重要。
