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. 2024 Jun 6:18:147-161.
doi: 10.2147/BTT.S448587. eCollection 2024.

Osteoimmune Interaction and TH-1/TH-2 Ratio in Jawbone Marrow Defects: An Underestimated Association - Original Research

Johann Lechner  1 , Volker von Baehr  2 , Florian Notter  1 , Fabian Schick  1
Affiliations

Osteoimmune Interaction and TH-1/TH-2 Ratio in Jawbone Marrow Defects: An Underestimated Association - Original Research

Johann Lechner et al. Biologics. .

Abstract

Introduction: 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.

Aim and objectives: 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.

Material and methods: 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.

Results: 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.

Discussion: 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.

Conclusion: 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.

Keywords: RANTES/CCL5; T-cells; Th1/Th2 shift; jawbone; osteoclastogenesis; osteoimmunology.

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Conflict of interest statement

Johann Lechner reports non-financial support from Digital Dental and Healthcare Technology (DDHT), during the conduct of the study. Johann Lechner is the holder of a patent used in the new TAU apparatus, CaviTAU®. The authors report no other conflicts of interest in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
Control of bone cells by immune cells through cytokine-mediated differentiation of Th1/Th2 cells (see red circle).
Figure 2
Figure 2
Areas of BMDJ/FDOJ.
Figure 3
Figure 3
Multiplex analysis (in pg/mL) of 27 cytokines in five BMDJ/FDOJ samples showing the singular overexpression of IL-1ra and RANTES/CCL5 with values extrapolated beyond the range of the multiplex device.
Figure 4
Figure 4
Cytoine expression in BMDJ/FDOJ samples for a seven cytokine panel.
Figure 5
Figure 5
Distribution of disorders for 197 patients with CID.
Figure 6
Figure 6
Diagram showing each of the three Th1/Th2 ratio groups: Th1/Th2 ratio above 21, Th1/Th2 ratio normal reference range 6.1 to 21 and Th1/Th2 ratio below 6.1.
Figure 7
Figure 7
Diagram of the two patient groups with a low Th1/Th2 ratio and corresponding IL-10 (T-reg) underexpression of 480 pg/mL and IL-10 (T-reg) overexpression of 2.400 pg/mL out of the normal reference range of IL-10 (T-reg) of 760 to 1900 pg/mL.
Figure 8
Figure 8
Analysis of the Th1/Th2 ratio and T-reg profile of 197 CID patients with clinically defined BMDJ/FDOJ as compared to normal values for the Th1/Th2 ratio and normal range of T-reg.
Figure 9
Figure 9
Comparison of the cytokine analyses of 128 BMDJ/FDOJ samples.
Figure 10
Figure 10
In addition to the systemic immune imbalance found in the study cohort (see Figure 8), there was also a local Th2 shift and corresponding low IFN-y in BMDJ/FDOJ areas.
See this image and copyright information in PMC

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