We present data here from mechanistic studies using T- and B-lymphocyte-independent arthritis models, indicating (i) the IL-23p19 subunit cellular source and responsive cell type, (ii) further evidence in inflammation for a possible interdependence between IL-23 and other cytokines, namely TNF, GM-CSF and CCL17 and (iii) importantly, the successful therapeutic blockade of arthritic pain and disease with a neutralizing anti-IL-23p19 subunit mAb consistent with a peripheral action of IL-23 in the control of ongoing pain and disease. This evidence concerns the gene IL23A and arthritic joint disease.