Lechner Johann, von Baehr Volker, Notter Florian, Schick Fabian
Clinic for Integrative Dentistry, Munich, Germany.
Department of Immunology and Allergology, Institute for Medical Diagnostics, Berlin, Germany.
Biologics. 2024 Jun 6;18:147-161. doi: 10.2147/BTT.S448587. eCollection 2024.
Osteoimmunology recognizes the relationship between bone cells and immune cells. Chronic osteoimmune dysregulation is present in bone marrow defects of the jaw (BMDJ) as fatty-degenerative osteonecrosis (FDOJ). In comparison to samples from healthy jaw bone, the cytokine analysis of samples of BMDJ/FDOJ from 128 patients showed downregulated TNF-α and IL-6 expression and the singular overexpression of the chemokine RANTES/CCL5.
This paper raises the question of whether the osteoimmune defects due to incomplete wound healing in BMDJ/FDOJ in 128 patients are related to dysregulation of the Th1/Th2 ratio and regulatory T cell (T-reg) expression in a control group of 197 BMDJ/FDOJ patients, each presenting with BMDJ/FJOD and one of seven different immune disorders.
In the control group, serum concentrations of the cytokines IFN-y and IL-4 were determined after stimulated cytokine release and displayed as Th1/Th2 ratios.
Data show a shift in Th2 in more than 80% (n = 167) of the control cohort of 197 chronically ill patients with concomitant BMDJ/FDOJ. In these 167 subjects, the Th1/Th2 ratio was <6.1 demonstrating impaired immune regulation. Forty-seven subjects or 30% showed not only a shift in Th2 but also excessive T-reg overactivation with levels of >1.900 pg/mL, indicating strongly downregulated immune activity.
BMDJ/FDOJ is characterized by a lack of Th1 cytokines and an excessive expression of RANTES/CCL5 and IL-1ra and, thus, the inversion of an acute inflammatory cytokine pattern. In contrast, abdominal fat contains a very high proportion of regulatory Th1 cells and produces an inflammatory immune response through the high overexpression of TNF-α and IL-6. The lack of Th1 activation in BMDJ/FDOJ areas inhibits normal wound healing and supports the persistence of BMDJ/FDOJ.
The Th1/Th2 ratio requires greater consideration, especially with respect to wound healing following dental surgical interventions, such as jaw surgery, implantation and augmentation, to avoid the emergence of the osteoimmune situation that is characteristic of BMDJ/FDOJ.
骨免疫学认识到骨细胞与免疫细胞之间的关系。慢性骨免疫失调存在于颌骨骨髓缺损（BMDJ）中，表现为脂肪变性骨坏死（FDOJ）。与健康颌骨样本相比，对128例患者的BMDJ/FDOJ样本进行的细胞因子分析显示，肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）表达下调，趋化因子调节激活正常T细胞表达和分泌因子（RANTES/CCL5）单独过度表达。
本文提出一个问题，即128例患者因BMDJ/FDOJ伤口愈合不完全导致的骨免疫缺陷，是否与197例BMDJ/FDOJ患者对照组中辅助性T细胞1/辅助性T细胞2（Th1/Th2）比例失调和调节性T细胞（T-reg）表达有关，这些患者均患有BMDJ/FJOD及七种不同免疫疾病之一。
在对照组中，刺激细胞因子释放后测定细胞因子干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）的血清浓度，并以Th1/Th2比值表示。
数据显示，在197例患有BMDJ/FDOJ的慢性病患者的对照组中，超过80%（n = 167）的患者出现Th2偏移。在这167名受试者中，Th1/Th2比值<6.1，表明免疫调节受损。四十七名受试者（30%）不仅出现Th2偏移，而且T-reg过度激活，水平>1900 pg/mL，表明免疫活性严重下调。
BMDJ/FDOJ的特征是缺乏Th1细胞因子，RANTES/CCL5和白细胞介素-1受体拮抗剂（IL-1ra）过度表达，从而使急性炎症细胞因子模式发生倒置。相比之下，腹部脂肪中调节性Th1细胞比例非常高，并通过肿瘤坏死因子-α和白细胞介素-6的高度过度表达产生炎症性免疫反应。BMDJ/FDOJ区域缺乏Th1激活会抑制正常伤口愈合，并促使BMDJ/FDOJ持续存在。
Th1/Th2比值需要更多关注，特别是在牙外科手术（如颌骨手术、植入和增大手术）后的伤口愈合方面，以避免出现BMDJ/FDOJ特有的骨免疫情况。
