Publications by Author: Ran Gu

Interleukin 27 has both pro-inflammatory and anti-inflammatory properties in autoimmunity. The anti-inflammatory effects of IL-27 are linked with inhibition of Th17 differentiation but the IL-27 effect on myeloid cells is less studied. Herein we demonstrate that IL-27 inhibits IL-23-induced inflammation associated not only with Th17 cells but also with myeloid cell infiltration in the joints and splenic myeloid populations of CD11b+ GR1+ and CD3-CD11b+CD11c-GR1- cells. The IL-27 anti-inflammatory response was associated with reduced levels of myeloid cells in the spleen and bone marrow. Overall, our data demonstrate that IL-27 has an immunosuppressive role that affects IL-23-dependent myelopoiesis in the bone marrow and its progression to inflammatory arthritis and plays a crucial role in controlling IL-23 driven joint inflammation by negatively regulating the expansion of myeloid cell subsets.

OBJECTIVE: To investigate the role of interleukin-23 (IL-23) in pathologic bone remodeling in inflammatory arthritis.

METHODS: In this study we investigated the role of IL-23 in osteoclast differentiation and activation using in vivo gene transfer techniques in wild-type and myeloid DNAX-activation protein 12-associating lectin-1 (MDL-1)-deficient mice, and by performing in vitro and in vivo osteoclastogenesis assays using spectral flow cytometry, micro-computed tomography analysis, Western blotting, and immunoprecipitation.

RESULTS: Herein, we show that IL-23 induces the expansion of a myeloid osteoclast precursor population and supports osteoclastogenesis and bone resorption in inflammatory arthritis. Genetic ablation of C-type lectin domain family member 5A, also known as MDL-1, prevents the induction of osteoclast precursors by IL-23 that is associated with bone destruction, as commonly observed in inflammatory arthritis. Moreover, osteoclasts derived from the bone marrow of MDL-1-deficient mice showed impaired osteoclastogenesis, and MDL-1-/- mice had increased bone mineral density.

CONCLUSION: Our data show that IL-23 signaling regulates the availability of osteoclast precursors in inflammatory arthritis that could be effectively targeted for the treatment of inflammatory bone loss in inflammatory arthritis.