التفاصيل البيبلوغرافية
| العنوان: |
HTLV‐1 infected T cells cause bone loss via small extracellular vesicles. |
| المؤلفون: |
Pokhrel, Nitin Kumar, Panfil, Amanda R., Habib, Haniya, Seeniraj, Shamreethaa, Joseph, Ancy, Rauch, Daniel, Cox, Linda, Sprung, Robert, Gilmore, Petra Erdmann, Zhang, Qiang, Townsend, Robert Reid, Yu, Lianbo, Yilmaz, Ayse Selen, Aurora, Rajeev, Park, William, Ratner, Lee, Weilbaecher, Katherine N., Veis, Deborah J. |
| المصدر: |
Journal of Extracellular Vesicles; Oct2024, Vol. 13 Issue 10, p1-14, 14p |
| مصطلحات موضوعية: |
VIRAL proteins, SYNTAXINS, T cells, CYTOKINE receptors, BONE cells, BONE resorption |
| مستخلص: |
Adult T cell leukaemia (ATL), caused by infection with human T‐ lymphotropic virus type 1 (HTLV‐1), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient‐derived ATL cells (ATL‐PDX) and HTLV‐1 immortalized CD4+ T cell lines (HTLV/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV/T leads to a profound local decrease in bone mass similar to marrow‐replacing ATL‐PDX, despite the fact that few HTLV/T cells persisted in the bone. To study the direct effect of HTLV/T and ATL‐PDX on osteoclasts, supernatants were added to murine and human osteoclast precursors. ATL‐PDX supernatants from hypercalcemic patients promoted the formation of mature osteoclasts, while those from HTLV/T were variably stimulatory, but had largely consistent effects between human and murine cultures. Interestingly, this osteoclastic activity did not correlate with expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa‐B ligand (RANKL), suggesting an alternative mechanism. HTLV/T and ATL‐PDX produce small extracellular vesicles (sEV), known to facilitate HTLV‐1 infection. We hypothesized that these sEV also mediate bone loss by targeting osteoclasts. We isolated sEV from both HTLV/T and ATL‐PDX, and found they carried most of the activity found in supernatants. In contrast, sEV from uninfected activated T cells had little effect. Analysis of sEV (both active and inactive) by mass spectrometry and electron microscopy confirmed absence of RANKL and intact virus. Viral proteins Tax and Env were only present in sEV from the active, osteoclast‐stimulatory group, along with increased representation of proteins involved in osteoclastogenesis and bone resorption. sEV from osteoclast‐active HTLV/T injected over mouse calvaria in the presence of low‐dose RANKL caused more osteolysis than osteoclast‐inactive sEV or RANKL alone. Thus, HTLV‐1 infection of T cells can cause release of sEV with strong osteolytic potential, providing a mechanism beyond RANKL production that modifies the bone microenvironment, even in the absence of overt leukaemia. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Extracellular Vesicles is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder