Distinct cross talk of IL-17 & TGF-ß with the immature CD11c+ TRAF6(-/-) -null myeloid dendritic cell-derived osteoclast precursor (mDDOCp) may engage signaling toward an alternative pathway of osteoclastogenesis for arthritic bone loss in vivo.
Immun Inflamm Dis
; 12(2): e1173, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38415924
ABSTRACT
BACKGROUND:
Dendritic cells (DCs), though borne heterogeneous, are the most potent antigen-presenting cells, whose critical functions include triggering antigen-specific naïve T-cell responses and fine-tuning the innate versus adaptive immunity at the osteo-immune and/or mucosal mesenchyme interface. We previously reported that immature myeloid-CD11c+ DCs/mDCs may act like osteoclast (OC) precursors (OCp/mDDOCp) capable of developing into functional OCs via an alternative pathway of inflammation-induced osteoclastogenesis; however, what are their contribution and signaling interactions with key osteotropic cytokines (i.e., interleukin-17 [IL-17] and transforming growth factor-ß [TGF-ß]) to bearing such inflammatory bone loss in vivo remain unclear to date.METHODS:
Herein, we employed mature adult bone marrow-reconstituted C57BL/6 TRAF6(-/-) -null chimeras without the classical monocyte/macrophage (Mo/MÏ)-derived OCs to address their potential contribution to OCp/mDDOCp-mediated osteoclastogenesis in the chicken type-II-collagen (CC-II)-induced joint inflammation versus arthritic bone loss and parallel associations with the double-positive CD11c+ TRAP+ TRAF6-null(-/-) DC-like OCs detected in vivo via the quantitative dual-immunohistochemistry and digital histomorphometry for analyses.RESULTS:
The resulting findings revealed the unrecognized novel insight that (i) immature myeloid-CD11c+ TRAF6(-/-) TRAP+ DC-like OCs were involved, co-localized, and strongly associated with joint inflammation and bone loss, independent of the Mo/MÏ-derived classical OCs, in CC-II-immunized TRAF6(-/-) -null chimeras, and (ii) the osteotropic IL-17 may engage distinct crosstalk with CD11c+ mDCs/mDDOCp before developing the CD11c+ TRAP+ TRAF6(-/-) OCs via a TGF-ß-dependent interaction toward inflammation-induced arthritic bone loss in vivo.CONCLUSION:
These results confirm and substantiate the validity of TRAF6(-/-) -null chimeras to address the significance of immature mCD11c+ TRAP+ DC-like OCs/mDDOCp subset for an alternative pathway of arthritic bone loss in vivo. Such CD11c+ mDCs/mDDOCp-associated osteoclastogenesis through the step-wise twist-in-turns osteo-immune cross talks are thereby theme highlighted to depict a summative re-visitation proposed.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoclastos
/
Osteogénesis
Límite:
Humans
Idioma:
En
Revista:
Immun Inflamm Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
Taiwán
Pais de publicación:
Reino Unido