Toll-like receptor 4 in bone marrow-derived cells as well as tissue-resident cells participate in aggravating autoimmune destructive arthritis

作者：van den Brand Ben T; Abdollahi Roodsaz Shahla; Bennink Miranda B; Bussink Johan; Arntz Onno J; van den Berg Wim B; van de Loo Fons A J^*

来源：Annals of the Rheumatic Diseases, 2013, 72(8): 1407-1415.

DOI：10.1136/annrheumdis-2012-202467

• Arthritis
• Autoimmunity
• Cytokines
• Inflammation
• T Cells

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2013-8