Oral Presentation 6th Australian Health and Medical Research Congress 2012

Inflammation in the periphery and dendritic cell progenitors in the bone marrow (#167)

Prue H Hart 1 , Royce LX Ng 1 , Deborah H Strickland 1 , Naomi M Scott 1
  1. University of Western Australia, Telethon Kids Institute, Perth, WA, Australia

This laboratory has previously shown that CD11c+ cells (dendritic cells, DCs) cultured from bone marrow of mice with inflammation of the skin (UV irradiation), airways (OVA-alum model of experimental allergic airways disease), or peritoneal cavity (intraperitoneal alum injection), have poor priming ability when transferred into naïve mice, and create a reduced antigen-specific memory response. The CD11c+ cells were also regulatory if injected into antigen-presensitised mice. Inflammation-associated prostaglandin E2 was involved directly or indirectly as the cyclooxygenase inhibitor, indomethacin, prevented the development from bone marrow of poorly priming/regulatory DCs. The regulatory ability was detected regardless of which growth factors were used to differentiate the bone marrow DC precursors in culture, including GM-CSF (± IL-4) or FLT3-L and suggested that the developmental pathway of an early DC committed cell was altered by prostaglandin E2-associated tissue inflammation. Bone marrow-ablated mice were engrafted with bone marrow cells from control mice and mice with skin inflammation. Sixteen weeks after bone marrow cell transfer, immune responses largely dependent on DC function were poor in recipients engrafted with cells from mice with skin inflammation. Contact hypersensitivity responses were significantly reduced. When an inflammatory antigen was painted onto skin, the inflammatory response was negligible. T lymphocytes from all chimeric mice had similar proliferative capabilities. These results suggest an effect of prostaglandin E2 on very early progenitors, possibly haemopoietic stem cells. Further, when pregnant mice were UV-irradiated (skin inflammation), the bone marrow of the progeny contained altered DC progenitors. Upon differentiation of the bone marrow cells, the priming ability of the CD11c+ cells was significantly reduced. This result suggests a possible epigenetic effect of UV irradiation on bone marrow DC progenitors. The effect of tissue inflammation on DC development may be an important homeostatic process that has potential for therapeutic use.