Background and objectives Macroautophagy is a major catabolic pathway that plays a key role in cellular homeostasis. Macroautophagy has been recently implicated in shaping the innate and adaptive immune responses via cytokine secretion and antigen presentation in various diseases. However the contribution of the pathway to autoimmune arthritis is still not established. Our aim was to address the role of macroautophagy in the adaptive immune response during antigen induced arthritis (AIA), using mice that are deficient in macroautophagy in their dendritic cells.

Materials and methods CD11c-Cre mice (C57BL/6), were crossed with Atg5^flox/flox mice (C57BL/6) resulting in the complete abolishment of a functional autophagy pathway in dendritic cells (DC/ATG5^-/-).

For AIA, mice were immunised with methylated BSA (mBSA) and CFA. Monoarthritis was induced at day 21. At day 28 animals were sacrificed. For histological scoring knees sections were stained with hematoxylin and eosin and toluidine blue. T cell function was monitored by cytokine production and CFSE staining.

For in vitro analysis, bone marrow derived dendritic cells (BMDC) were treated with TLR ligands. Cytokines production was quantified by ELISA, and co-stimulatory molecule expression analysed by flow cytometry.

Results Our results identified autophagy as a negative regulator of the inflammatory response during AIA. Indeed we found that in the absence of autophagy in dendritic cells AIA was more severe correlating with an enhanced Th1/Th17 response.

Histological analysis showed an enhanced inflammatory score, due to enhanced cartilage destruction and bone erosion in (DC/ATG5^-/-) mice. Interestingly, the Th1/Th17 response in DC/ATG5^-/- mice was significantly increased. Indeed lymph node cell cultures showed enhanced CD4 T cell proliferation with increased INF-gamma and IL-17 production. This was observed both in an antigen specific manner from ex vivo treatment with mBSA or with CD3/CD28 treatment.

In vitro analysis showed that in response to TLR activation DC/ATG5^-/- has enhanced IL-1B production, and higher expression of co-stimulatory molecules.

Conclusions Autophagy deficiency in dendritic cells exacerbates the Th1/Th17 inflammatory response in the AIA model, resulting in increased cartilage destruction and bone erosion. The precise in vivo mechanism behind this regulation is under investigation; however this might be in part due to enhanced IL-1β production and increased co-stimulatory molecule expression on antigen presenting cells.