Essential role of TNF-alpha in development of spleen fibroblastic reticular cells

TNF-alpha plays an important role in the development of secondary lymphoid tissues. Earlier studies showed that fibroblastic reticular cells express TNF-alpha receptor, suggesting that TNF-alpha may affect the development of FRCs. To test this, we analyzed the development and function of FRCs in wild-type or TNF-alpha knockout mice. We found that GP38 expression was down-regulated in the spleen of TNF-alpha knockout mice. Chemokines, mainly secreted by GP38+ FRCs, were also down-regulated. Additionally, we found that absence of TNF-alpha decreased the homing ability to direct T cells to the spleen. However, absence of TNF-alpha did not affect the development of lymph nodes FRCs. These data reveal that TNF-alpha plays an important role in the development of spleen FRCs. Absence of TNF-alpha could cause abnormality of spleen FRCs, thereby weakening the homing ability of T cells to localize to the spleen T cell zone.