@article {van den Brand1407, author = {Ben T van den Brand and Shahla Abdollahi-Roodsaz and Miranda B Bennink and Johan Bussink and Onno J Arntz and Wim B van den Berg and Fons A J van de Loo}, title = {Toll-like receptor 4 in bone marrow-derived cells as well as tissue-resident cells participate in aggravating autoimmune destructive arthritis}, volume = {72}, number = {8}, pages = {1407--1415}, year = {2013}, doi = {10.1136/annrheumdis-2012-202467}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objective A prominent role of Toll-like receptor 4 (TLR4) in arthritis is emerging. TLR4 is functional in immune cells and stromal cells. The aim was to investigate the involvement of TLR4 in bone marrow (BM)-derived and resident cells in arthritis. Methods Reciprocal sex-mismatched BM transplantation was performed between IL-1Ra-/-TLR4+/+ and IL-1Ra-/-TLR4-/- double knockout animals in Balb/c background. Arthritis was assessed macroscopically and by histopathology. Immunity was evaluated by splenic cytokine production and flow cytometry in draining lymph node (DLN) cells. Results Arthritis progression was reduced to a similar extent in animals lacking TLR4 on BM-derived, resident cells or both. Histology revealed that joint inflammation was partially TLR4-dependent in either BM-derived or resident cells. TLR4 plays an additive role in BM-derived and resident cells in promoting cartilage erosion. By contrast, TLR4 was equally important in BM-derived and resident cells in mediating bone erosion. Systemically, TLR4 in both BM-derived and resident cells contributed to IL-17 production by splenic T-cells, whereas in the DLNs of arthritic joints this was not the case. Interestingly, in DLN, the dominant cells producing IL-17 were CD4 negative, and cell numbers were determined by TLR4 in the BM-derived cells. Conclusions TLR4 is necessary in both BM-derived and resident cells for full-blown joint swelling, inflammation and bone erosion. Furthermore, TLR4 on BM-derived and tissue-resident cells show an additive effect in cartilage destruction. Interestingly, TLR4 on BM-derived and tissue-resident cells are both required for IL-17 production in spleen, but only in BM-derived cells in DLN.}, issn = {0003-4967}, URL = {https://ard.bmj.com/content/72/8/1407}, eprint = {https://ard.bmj.com/content/72/8/1407.full.pdf}, journal = {Annals of the Rheumatic Diseases} }