辅助性T细胞17与调节性T细胞之间的制衡效应调控口腔颌面部骨损伤修复的研究进展

Balance between T-helper 17 cells and regulatory T cells in bone remodeling and their impact on oral and maxillofacial damage recovery

摘要

骨损伤后的骨组织重塑直至最终修复，是一个受到严格调控的动态过程。其中，免疫系统的调控作用日益受到研究者们的重视。在诸多免疫细胞中，辅助性T细胞17（Th17）和调节性T细胞（Treg）分别以促炎和抑炎效应对骨代谢相关细胞的功能与活性发挥着重要的调控作用，Th17/Treg细胞平衡失调与多种骨代谢疾病密切相关，调节这一平衡可能为骨损伤修复提供新的策略。本文旨在对Th17与Treg细胞在骨重塑中的制衡调节机制，以及干预Th17/Treg细胞平衡以促进口腔颌面部骨损伤修复的研究现状作一综述。

Abstract

Bone tissue remodeling during bone injury recovery is a well-regulated dynamic process, of which the pro-minent role of immune balance on bone homeostasis is increasingly understood. Among the various immune cells, T-hel-per 17 cells (Th17) and regulatory T cells (Treg) have attracted considerable attention because of their contradictive roles in inflammatory response and bone homeostasis. The imbalance of the Th17/Treg cell balance is closely associated with va-rious bone metabolism disorders, and regulating this balance may provide novel strategies for bone injury repair. Thus, this review focuses on the balance between Th17 and Treg in bone remodeling and their impacts on oral and maxillofacial damage recovery.

关键词

辅助性T细胞17 / 调节性T细胞 / 细胞平衡 / 骨免疫 / 牙周炎 / 种植体周围炎

Key words

T-helper 17 cell / regulatory T cell / cell balance / osteoimmunology / periodontitis / peri-implantitis

炎症性骨吸收、机械损伤、肿瘤、生理性萎缩均会引起口腔颌面部骨损伤，这些局部病变与全身健康状态紧密相关，若未能及时予以纠正，会对全身健康产生进一步的不良影响^[1-3]，因此，口腔颌面部的骨损伤修复一直是研究的热点领域。骨损伤的修复过程是一个骨重塑过程。在此过程中，骨相关细胞通过各种直接、间接信号传导机制^[4]，经历起始、吸收、逆转、形成和终止等阶段^[5]，是一个被严格调控的动态过程。骨重塑对骨稳态及损伤的成功愈合至关重要^[6-8]。随着骨免疫（osteoimmunology）这一概念的提出，强调了免疫系统在骨代谢中的重要作用^[9]，进而越来越多的研究揭示了各种免疫细胞的变化及相互平衡通过影响骨相关细胞，积极参与骨生理和病理过程。

本文旨在对辅助性T细胞17（T-helper 17 cell，Th17）和调节性T细胞（regulatory T cell，Treg）在骨重塑中的制衡调节机制及利用该机制促进口腔颌面部骨损伤修复的研究现状进行综述。

1　 免疫系统在骨损伤修复前期的作用

骨损伤会导致局部出现大量细胞碎片、微生物等坏死组织与感染物质，在进行有序的骨重塑前，清除局部感染、坏死物质，创造合适的骨修复微环境十分重要，免疫系统在这一过程中发挥着主导作用。

当病原体或损伤出现时，免疫系统通过模式识别受体（pattern recognition receptor，PRR）识别病原体相关分子模式（pathogen-associated molecular pattern，PAMP）或损伤相关分子模式（damage-associated molecular pattern，DAMP），刺激补体系统启动一系列基于蛋白酶的裂解和激活过程，招募并激活固有免疫系统中的中性粒细胞、巨噬细胞等发挥吞噬作用，并释放炎症介质，吸引更多的免疫细胞到损伤或感染部位^[10-11]。

中性粒细胞作为首批到达损伤或感染部位的固有免疫细胞，利用PRR识别PAMP、DAMP后，可以多种方式对局部进行清理，除发挥吞噬作用外，还可通过呼吸爆发产生活性氧（reactive oxygen species，ROS）以杀死和分解不良物质；也可以释放中性粒细胞胞外陷阱（neutrophil extracellular trap，NET）来捕获和限制不良物质，以防止其扩散。然而，过度的炎症反应可能会加剧局部组织损伤。如牙周炎加剧即可与此相关^[12]。近来，有学者提出了中性粒细胞功能极化概念，即中性粒细胞可区分为促炎性N1亚群和抑炎性N2亚群。二者在对抗牙周病病原微生物中都发挥着重要作用^[13-14]。而牙周炎加重可能与N1亚群过度活跃有关。这些促炎性中性粒细胞促进NET、脱颗粒和促炎细胞因子的大量产生，加剧局部牙龈组织与牙槽骨的破坏，而导致疾病加重^[12]。这一例证提示了中性粒细胞功能的复杂性，在某些条件下，中性粒细胞既是抵御感染的防御者，也是疾病加重的潜在驱动因素。中性粒细胞与牙周致病菌的相互作用可以导致免疫颠覆，甚至形成导致牙周炎恶化的免疫失调环境。中性粒细胞在牙周炎中存在着保护和破坏的双重功能，在其他骨损伤后的免疫反应中也可能存在着类似作用^[15]。

紧随中性粒细胞之后，巨噬细胞达到损伤部位，吞噬细胞残骸和病原体，并释放更多炎症介质，进一步促进炎症反应和免疫细胞的招募。近年，巨噬细胞对骨骼系统的影响越来越受到重视。在单核细胞趋化蛋白（monocyte chemoattractant protein，MCP）-1的作用下^[16]，巨噬细胞聚集与血凝块中的血小板释放大量活性物质，如肿瘤坏死因子（tumor necrosis factor，TNF）-α、白细胞介素（interleukin，IL）-1、转化生长因子（transforming growth factor，TGF）-β超家族蛋白、血小板衍生生长因子、碱性成纤维细胞生长因子、胰岛素样生长因子等，这些细胞因子会促进间充质干细胞向成骨、成软骨相关功能性细胞分化，并促进血管新生和组织修复^[17-18]。

巨噬细胞在响应局部微环境刺激时表现出显著的功能可塑性和异质性^[19]。M1型巨噬细胞通过释放IL-23、TNF-α和ROS等促炎症细胞因子，具有更强的抗原呈递能力和促炎特性。相反，M2型巨噬细胞分泌免疫抑制细胞因子和血管生成因子，缓和炎症反应，启动组织修复过程，并最终增强成骨作用^[20]。巨噬细胞M1/M2极化状态的转化是从炎症状态转变为组织修复状态的关键^[21-22]。大量研究^[23-25]表明，在骨组织工程中有针对性地调节M2型巨噬细胞，可创造利于骨修复的免疫微环境，是促进成骨的有效策略。

在损伤前期，免疫系统的作用主要是补体系统、中性粒细胞和巨噬细胞等固有免疫细胞的聚集和激活，通过多种形式清除损伤部位的微生物和细胞碎片，同时也通过分泌因子，调整极化状态等方式招募间充质干细胞、促进血管再生，为骨愈合奠定基础。同时，活化的固有免疫细胞通过抗原提呈，协同并分泌细胞因子，启动适应性免疫应答，促进淋巴细胞活化、增殖和分化。

2　 免疫系统对骨损伤修复微环境的决定性影响

骨系统与免疫系统之间的密切联系早已得到关注^[26]。随着Arron等^[9]将骨免疫定义为研究骨重塑细胞和免疫细胞之间相互作用的一门学科，强调了免疫系统在骨代谢中的重要作用。经过免疫系统对骨损伤后的局部微环境进行初步清理，免疫系统继续为骨修复的促进创造条件。免疫细胞通过影响骨相关细胞，积极参与骨生理和病理过程，其中涉及了许多免疫细胞的变化及相互平衡。在诸多免疫细胞中，Th17细胞与Treg细胞因其在免疫反应中的双重调节作用，尤其与骨代谢和炎症性骨疾病密切相关，因此备受关注。

Th17细胞是辅助型T细胞亚群之一，它的分化受到抗原呈递细胞产生IL-6、TGF-β1和IL-23的促进^[27-28]，功能受转录调节因子孤核受体（reti-noic acid-related orphan receptor γt，RORγt）的调控^[29]。一些学者^[30-31]发现了Treg细胞，并发现其在维持免疫耐受和骨稳态中发挥关键作用。Treg细胞在IL-2和TGF-β1的存在下分化形成，并表达表型特异性转录因子叉头盒P3（forkhead box P3，Foxp3）。Foxp3目前被认为是Treg细胞的特异性鉴定标记，也是激活和抑制Treg细胞功能的重要分子。Th17和Treg细胞从同一类型的初始T细胞分化而来，在特定的细胞因子微环境下可以相互转化^[32]。其中，TGF-β在Th17与Treg细胞分化中具有关键作用。TGF-β在无IL-6条件下，主要诱导初始T细胞向Treg细胞分化（以下简称Treg细胞分化）；而在IL-6存在时，TGF-β会促进初始T细胞向Th17细胞分化（以下简称Th17细胞分化）^[33-34]。Th17细胞与Treg细胞之间的制衡效应具体可以体现在3个方面：分化上相互抑制、功能上相互拮抗，以及失衡导致的继发病理损害。

Th17细胞的分化主要依赖于RORγt这一转录因子，而Treg细胞的分化主要由Foxp3主导。RORγt和Foxp3在细胞核内竞争性地相互抑制对方的功能。如Foxp3可直接抑制RORγt的转录功能，从而抑制Th17细胞的分化^[35]。Th17和Treg细胞在代谢层面同样存在相互抑制关系。Th17细胞偏好糖酵解途径，而Treg细胞则依赖脂肪酸氧化。不同的代谢途径支持不同细胞的分化并抑制对方的功能。如丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）有助于促进Treg细胞的代谢活动，而糖酵解途径的增加则有利于Th17细胞分化^[36]。Th17与Treg细胞在功能上是相互拮抗体，Th17细胞通过分泌促炎细胞因子，促进炎症反应；而Treg细胞则通过分泌抗炎细胞因子，抑制炎症反应。两者在特定条件下互相抑制，维持免疫反应的平衡。在正常情况下，Th17与Treg之间的平衡维持免疫系统的稳定。若这种平衡被打破，如Th17细胞过度活化或Treg细胞功能异常，就可能导致自身免疫性疾病或慢性炎症。而大量研究^[37-41]也关注到Th17和Treg细胞对骨骼系统的影响。如学者们^[42]探究种植体周围炎骨免疫发病机制时发现：与健康组织相比，种植体周围炎周围组织中转录因子RORγt和Foxp3的基因表达水平较高。还有研究^[43]进一步证明了Th17与Treg细胞是种植体周围炎引起骨代谢异常的关键因素。牙槽骨的代谢平衡依赖于Th17/Treg细胞活性之间的相互关系。病理性牙槽骨吸收是Th17/Treg失衡的结果^[44-45]。

下文将重点讨论 Treg/Th17细胞平衡与间充质干细胞、成骨细胞、破骨细胞之间的关系。

2.1　 Th17细胞对破骨细胞、间充质干细胞、成骨细胞的作用

有学者^[46-47]认为，Th17是免疫反应影响骨稳态的最可能因素之一。活化的Th17细胞能产生多种细胞因子^[48-49]，其中IL-17是Th17细胞的标志性产物^[50]。

众所周知，IL-17被认为是促进破骨细胞活性的促炎细胞因子^[51]，与侵蚀性关节炎、牙周炎等疾病造成炎症性骨丢失有关^[52-53]。背后的机制主要涉及直接或间接影响核因子κB受体激活因子（receptor activator of nuclear factor-κB，RANK）-核因子κB受体激活因子配体（receptor activator of nuclear factor-κB ligand，RANKL）这一对促进破骨细胞分化和活化的信号分子^[54]。

Th17可以通过分泌IL-17诱导成骨细胞分泌RANKL^[55]，并且增加破骨细胞表面的RANK表达以加强对RANKL刺激的反应性^[56]。同时，Th17细胞也可直接表达RANKL^[47]，通过上调RANKL/骨保护素（osteoprotegerin，OPG）比例实现促进破骨细胞的生成与功能^[57]。RANKL与RANK的结合，激活细胞内信号转导途径。这些途径涉及多个适应子蛋白，其中包括肿瘤坏死因子受体相关因子6（tumor necrosis factor receptor-associated factor 6，TRAF6）。TRAF6的激活进一步启动一系列下游信号通路，包括核因子κB（nuclear factor kappa B，NF-κB）和MAPK信号通路，对破骨细胞的形成、存活、功能至关重要^[58]。

除了上述信号通路之外，也有学者关注到了IL-17通过控制破骨细胞能量代谢来影响其分化的作用。

具体而言，IL-17增加了骨髓来源巨噬细胞的能量代谢，并促进其向破骨细胞分化。这种调节是谷氨酰胺（glutamine，Glu）依赖性的，阻断Glu转运可以抑制IL-17诱导的破骨细胞活化和骨丢失^[59]。这一机制有望为逆转骨质疏松症患者的骨丢失提供一种新的干预策略^[60]。

与上述熟知的IL-17促炎破骨作用相反，IL-17可能也在骨稳态中发挥保护作用^[57]。IL-17对间充质细胞的增殖及随后分化为成骨细胞的促进作用，已在几项涉及小鼠模型或是使用人类血液制品的实验中得到证实^[61-65]。究其背后的机制，可能涉及ROS和转录激活因子1（activator of transcription 1，Act1）^[57]。也可能是IL-17通过促进矿化结节的形成和增加Runt相关转录因子2（Runt-related transcription factor 2，Runx2）表达来实现^[66]。还可能与IL-17能增加成骨细胞抵抗铁死亡的能力，从而促进成骨分化有关，其中涉及磷酸化信号转导子和转录激活子3（phosphorylated signal transducer and activator of transcription 3，p-STAT3）与核因子E2相关因子2（nuclear factor erythroid 2-related factor 2，NRF2）的相互作用^[67]。

然而，在大鼠模型中，IL-17并不能表现出促成骨的作用^[68]。探讨关于IL-17对于间充质干细胞、成骨细胞产生积极或消极影响的原因，有学者^[57]认为与IL-17受体亚型在不同物种中的差异表达相关。IL-17受体家族由IL-17RA至IL-17RE组成^[69]。IL-17RA、IL-17RC是人类间充质干细胞和小鼠颅骨细胞中2种最高表达的亚型，而大鼠颅骨细胞中的主要受体亚型为IL-17R B、D和E。因此，IL-17的促成骨作用可能通过IL-17RA/IL-17RC复合物介导完成。也有学者^[61]推测，IL-17只在早期愈合阶段发挥正向调节成骨发生的作用，具体原因仍有待进一步研究。

除了IL-17，Th17细胞还能直接或间接产生其他具有强烈促炎作用的细胞因子^[48-49,70]。其中，TNF-α能够激活多种信号通路，对骨骼系统产生负面影响。TNF-α介导巨噬细胞和B细胞RANKL的上调表达，从而激活并增强NF-κB和SAPK/JNK（stress-activated protein kinase/c-Jun NH₂-terminal kinase）这2种对破骨细胞至关重要的信号通路，达到促进破骨细胞生成的作用^[71-72]。同时，TNF-α还可通过增强Wnt信号通路抑制剂Dickkopf相关蛋白1（Dickkopf-related protein 1，DKK1）的表达影响成骨细胞^[73-74]。并且增加嘌呤受体P2Y2表达来促进成骨细胞凋亡^[75]。综合作用下，Th17促进破骨细胞，抑制成骨细胞，骨稳态呈现向骨吸收方面倾斜的趋势。

Th17在骨免疫中的作用及相关机制总结如表1^{[47,56-58,60-63,66-68,70-75]}。

2.2　 Treg细胞对破骨细胞、间充质干细胞、成骨细胞的作用

Treg细胞不仅可以通过分泌抗炎细胞因子IL-10、IL-4、IL-35和TGF-β来抑制Th17细胞的分化，还可以通过直接接触和（或）分泌细胞因子等途径，多方面影响破骨细胞的生成、功能及凋亡，抑制炎症反应和骨吸收^[41,76]。

如Treg细胞可以通过分泌IL-10减少核因子AT c1（nuclear factor of activated T cells, cytoplasmic 1，NFATc1）在巨噬细胞内的表达。与其他细胞分泌的RANKL和巨噬细胞集落刺激因子（macrophage colony-stimulating factor，M-CSF）共同作用，抑制巨噬细胞向破骨细胞分化^[77]，同时抑制破骨细胞前体细胞（osteoclast precursor cell，OCP）成熟为功能性破骨细胞^[78-79]。Treg细胞也可以利用细胞毒性T淋巴细胞抗原-4（cytotoxic T-lymphocyte antigen-4，CTLA4）通过与OCP上的CD80/CD86结合，促进OCP凋亡^[41,80]。还有研究^[81]发现：Treg细胞分泌的TGF-β1会诱导破骨细胞凋亡，机制主要涉及Smad途径，但也包括可能与细胞凋亡内部调节器相干扰的其他途径，如MAPK和Bcl2家族成员。

除了影响破骨细胞的生成与凋亡，Treg细胞也控制着破骨细胞的功能。在骨组织炎症期间，Treg细胞可以及时对细胞外刺激做出反应，进而调节破骨细胞功能，避免破骨细胞反应过度^[76]。

Treg来源与其他细胞来源的TGF-β1对破骨细胞共同发挥影响，其机制十分复杂。TGF-β1在破骨细胞自身也有合成、分泌，并对其功能活性起促进作用^[82]。有研究^[83]显示：TGF-β信号转导被阻断时，TRAF6-TAB1-TAK1复合物的形成受到抑制。抑制TRAF6-TAB1-TAK1复合物与Smad3的结合对于RANKL诱导的破骨细胞信号传导至关重要。因此，作为破骨细胞生成的重要自分泌因子^[84]，TGF-β被证明在RANKL诱导的破骨细胞形成中必不可少。

学者们根据体外研究中所观察到的，TGF-β1对破骨细胞双重影响的深层原因做出了一些推测。有学者^[85]认为，TGF-β对破骨细胞分化的双向影响，取决于Smad3或Smad1信号转导。已知TGF-β与受体结合后激活下游Smad蛋白。激活的Smad蛋白转入核内，调节不同的基因表达^[86]。研究^[85]发现：Smad3和Smad1信号分别诱导和抑制RANK的表达。也有学者^[87-88]将其归结为TGF-β1浓度的原因，即低浓度的TGF-β1会促进RANKL或TNF-α刺激的破骨细胞分化，而高水平的TGF-β1通过增强细胞培养物中成骨细胞分泌OPG来抑制破骨细胞的分化。体内状态下的真实原因有待进一步深入探索。

Treg细胞对间充质干细胞、成骨细胞也有一定的影响。Treg细胞通过分泌TGF-β，同时激活MAPK和Smad相关蛋白等细胞内效应物，诱导间充质干细胞成骨向分化^[89-92]。通过磷脂酰肌醇3激酶（phosphoinositide 3-kinase，PI3K）/蛋白激酶B（protein kinase B，AKT）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）/S6激酶1信号通路促进成骨细胞的存活和迁移^[93]。Treg细胞还可以促进NFAT1-SMAD3转录复合物在CD8⁺T细胞中的组装，从而驱动Wnt10b的表达，激活成骨细胞中的Wnt信号，促进成骨等^[94-95]。除此之外，TGF-β1具有软骨诱导的作用，可以抑制软骨的吸收^[96]。

Treg在骨免疫中的作用及相关机制总结详见表2^{[41,77-78,80-81,83,90,92-93,95-96]}。

在免疫系统中，与Th17/Treg细胞平衡共同发挥骨稳态调节作用的机制还有很多，如M1/M2巨噬细胞平衡、Th1/Th2细胞平衡、Th22/Breg平衡、γδ T细胞/αβ T细胞平衡等。这些细胞平衡通过一系列复杂的细胞因子、细胞表面分子和信号通路相互作用^[41]，对营造健康的免疫微环境，维护骨稳态、促进骨骼改建与修复具有重要意义^[97-99]。活化的淋巴细胞与固有免疫细胞相互作用、相互协调，消除病原微生物及其代谢产物的影响，共同促进炎症消散、吸收，最终恢复机体的正常功能^[100]。

3　 干预Th17/Treg细胞平衡以促进口腔颌面部骨损伤修复的研究现状

Th17和Treg细胞之间的平衡被认为是影响局部炎症反应和骨重塑的重要机制。Th17/Treg细胞比例失衡是牙周炎、种植体周围炎等多种疾病中导致或加重骨损伤的重要原因之一^[101-102]。认识到这个平衡对于骨愈合的作用，越来越多的学者开始尝试通过影响这一细胞平衡来促进骨修复。

牙周炎是一种发生在牙周支持组织中的慢性感染性疾病，主要由菌斑微生物引起。当菌群失衡时，宿主的免疫系统会产生反应，这种免疫反应在牙周组织破坏的各个阶段都发挥着至关重要的作用。Th17/Treg细胞比例失衡被认为是导致或加重牙槽骨损伤的主要因素之一^[103-104]。因此，近年来的研究主要集中于通过调节Th17/Treg细胞平衡，以达到治疗牙周炎并改善牙槽吸收的目的。

现有研究^[103]表明，改善局部的细胞因子环境，从而调节免疫炎症反应，恢复Th17/Treg细胞比例，对实验性牙周炎具有潜在的治疗效果。如局部或全身给药IL-35可以抑制实验性牙周炎小鼠的Th17/Treg失衡，并显著减少牙槽骨吸收^[45]。在此基础上，进一步研究^[105]发现，壳寡糖通过上调OPG、下调RANKL表达，调控OPG/RANKL/RANK通路，不仅有效恢复Th17/Treg免疫平衡，还显著改善了实验性牙周炎的临床症状。这一调控骨重塑相关蛋白的机制为治疗牙周炎提供了新的思路。

随着研究的深入，骨组织工程技术也逐渐成为调节Th17/Treg平衡的关键手段之一。负载小分子药物1,4-二氢苯并噻喃醌-4-酮-3-羧酸的水凝胶（1, 4-dihydrophenonthrolin-4-one-3-carboxylic acid，1,4-DPCA/hydrogel），通过上调低氧诱导因子1α和血管内皮生长因子A，展现了结合血管生成与成骨的活性^[106-107]，促进了CXC趋化因子受体4 （CXC chemokine receptor 4，CXCR4）依赖的Treg细胞积累，从而实现了牙槽骨再生，并在小鼠实验性牙周炎模型中成功恢复了骨质丢失^[108]。尽管局部注射1,4-DPCA/hydrogel用于人类牙周炎的疗效尚不明确，但有可能作为一种更方便、实用的治疗策略，值得未来研究。此外，负载TGF-β1和IL-10的免疫调节性树突状细胞在牙槽骨炎症部位具有高亲和力，其外泌体能够抑制Th17细胞的诱导，并促进Treg细胞的募集，从而减少骨破坏^[109]。初步实验提示外泌体在保护药物载体并延长其作用时间方面具有极大潜力。最后，从3D培养的间充质干细胞中获得的外泌体也显示出恢复Th17/Treg细胞平衡的能力，并有效解决了炎症牙周组织中的免疫失衡^[38]。

种植体周围炎与牙周炎具有相似的免疫反应和炎症表型^[110-111]。近年来，Th17/Treg细胞平衡失调作为促进种植体周围炎进展的关键因素受到了越来越多的关注^[42]。目前，机械和化学清创是种植体周围炎的标准治疗方法之一^[112]。清除种植体表面的细菌生物膜和炎症组织后，钛表面的骨重塑一直是种植体周围炎治疗的热门问题。清创使细菌生物膜和炎症组织被清除，种植体表面即可成为一个有利成骨的微环境^[113]。然而，有研究表明，清创诱导的钛表面变化可导致以免疫细胞促炎分化为特征的免疫失衡，具体而言，清创导致的钛表面形态改变可激活巨噬细胞和CD4⁺ T淋巴细胞，促使其分化为M1和Th17表型，产生促炎细胞因子等介质，不利于新骨形成。已有体外研究^[114]表明，免疫反应的促炎倾向可以被糖酵解抑制剂2-脱氧-D-葡萄糖（2-deoxy-D-glucose，2-DG）有效逆转，从而使局部免疫微环境由破骨倾向转化为成骨倾向，这为未来种植体周围炎的治疗提供了新的可能。

4　 总结与展望

综上所述，在骨重塑的早期阶段，免疫系统负责清除炎症性骨吸收、外伤性骨折、肿瘤和种植手术等引发的细胞碎片和微生物，为后续骨修复过程奠定基础。随后，免疫系统通过调节不同免疫细胞间的平衡，进一步维护这一微环境以促进骨重塑。在众多免疫细胞中，Th17和Treg细胞分别以促炎和抑炎效应对骨代谢相关细胞的功能与活性发挥着重要的调控作用。本文对Th17与Treg细胞在口腔颌面部创伤后骨重塑中制衡调节机制的研究进展进行了综述，旨在深入理解这2种细胞在骨修复过程中的复杂作用，并探讨其在口腔颌面部骨重塑的潜在应用。

Th17和Treg细胞对于成骨、破骨的作用并非绝对，可能受到作用时间、物种类别、受体种类等因素影响而动态变化。不同细胞因子、信号分子存在交互作用，机制细节有待进一步厘清。现有研究中，调节Th17与Treg细胞制衡机制在口腔颌面部骨重塑的应用研究还较为有限，大多数研究集中于牙周炎和种植体周围炎，更广泛的应用尚待进一步探索，以更好满足临床治疗需要。

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