IL-27 Modulates the Cytokine Secretion in the T Cell-Osteoclast Crosstalk During HIV Infection

Area of Science:

• Immunology
• Bone Biology
• Virology

Background:

• Chronic immune activation and inflammation in People with HIV (PWH) increase comorbidity risk, including bone loss.
• T cells and osteoclasts (OCs) play critical roles in regulating bone homeostasis.
• The cytokine Interleukin-27 (IL-27), part of the IL-12 family, modulates T cell cytokine profiles, but its function in HIV is understudied.

Purpose of the Study:

• To investigate the impact of OCs on T cell cytokine secretion in the context of HIV.
• To determine if IL-27 can modulate OC-influenced T cell functions.

Main Methods:

• Co-culture systems involving T cells and OCs from People with HIV (PWH) and healthy controls.
• Measurement of cytokine secretion (IFNγ, TNFα, IL-17, IL-10) and surface marker expression (RANKL) on T cells.

Main Results:

• OCs significantly enhanced secretion of IFNγ, TNFα, IL-17, RANKL, and IL-10 by T cells in both PWH and healthy individuals.
• In PWH, IL-27 treatment inhibited IL-17 secretion from T cells.
• IL-27 also downregulated the surface expression of RANKL on CD4 T cells in PWH.

Conclusions:

• Osteoclasts significantly influence T cell cytokine production, impacting bone homeostasis.
• In HIV infection, IL-27 may promote pro-inflammatory cytokines like IFNγ and TNFα at bone remodeling sites.
• IL-27 demonstrates immunomodulatory effects on T cells in the context of HIV, potentially influencing bone health.