PMID- 38415924 OWN - NLM STAT- MEDLINE DCOM- 20240229 LR - 20240301 IS - 2050-4527 (Electronic) IS - 2050-4527 (Linking) VI - 12 IP - 2 DP - 2024 Feb TI - Distinct cross talk of IL-17 & TGF-beta 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. PG - e1173 LID - 10.1002/iid3.1173 [doi] LID - e1173 AB - BACKGROUND: Dendritic cells (DCs), though borne heterogeneous, are the most potent antigen-presenting cells, whose critical functions include triggering antigen-specific naive 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-beta [TGF-beta]) 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/Mvarphi)-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/Mvarphi-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-beta-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. CI - (c) 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. FAU - Liu, Yen Chun G AU - Liu YCG AD - Department of Oral Hygiene, Center for Osteo-immunology & Biotechnology Research (COBR), College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - School of Oral Hygiene & Nursing, and School of Dentistry, Kanagawa Dental University (KDU), Yokosuka, Kanagawa, Japan. FAU - Teng, Andy Yen-Tung AU - Teng AY AUID- ORCID: 0000-0002-9977-190X AD - The Eastman Institute for Oral Health (EIOH), School of Medicine & Dentistry, University of Rochester, Rochester, New York, USA. AD - Center for Osteo-immunology & Biotechnology Research (COBR), School of Dentistry, College of Dental Medicine, Kaohsiung Medical University (KMU) and KMU-Hospital, Kaohsiung, Taiwan. LA - eng GR - NHRI-EX101-9946SI/National Health Research Institute, Taiwan/ PT - Journal Article PL - England TA - Immun Inflamm Dis JT - Immunity, inflammation and disease JID - 101635460 RN - 0 (Interleukin-17) RN - 0 (TNF Receptor-Associated Factor 6) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Humans MH - *Osteoclasts MH - *Osteogenesis MH - Interleukin-17 MH - TNF Receptor-Associated Factor 6/genetics MH - Transforming Growth Factor beta MH - Dendritic Cells MH - Inflammation PMC - PMC10851637 OTO - NOTNLM OT - IL-17 & TGF-beta OT - alternative pathway of osteoclastogenesis OT - arthritic bone loss OT - osteo-immune interactions OT - osteoclast versus CD11c+-myeloid dendritic cell derived osteoclast precursor (mDDOCp) COIS- The authors declare no conflicts of interest. EDAT- 2024/02/28 12:43 MHDA- 2024/02/29 06:43 PMCR- 2024/02/08 CRDT- 2024/02/28 09:51 PHST- 2024/01/18 00:00 [revised] PHST- 2023/07/30 00:00 [received] PHST- 2024/01/18 00:00 [accepted] PHST- 2024/02/29 06:43 [medline] PHST- 2024/02/28 12:43 [pubmed] PHST- 2024/02/28 09:51 [entrez] PHST- 2024/02/08 00:00 [pmc-release] AID - IID31173 [pii] AID - 10.1002/iid3.1173 [doi] PST - ppublish SO - Immun Inflamm Dis. 2024 Feb;12(2):e1173. doi: 10.1002/iid3.1173.