Follicular dendritic cell migration is promoted by the expression of matrix metalloproteinase 3 through TNFα-ERK1/2-AP-1 signaling

Abstract

Abstract Follicular dendritic cells (FDCs) are the major stromal components in the germinal center and are developed and maintained by lymphotoxin α1/β2 and tumor necrosis factor-α (TNFα). These cells have the pivotal role in high-affinity antibody production. However, many functions of FDCs are still unknown, such as its migration. Here, we demonstrate for the first time that TNFα increased matrix metalloproteinase 3 (MMP3) expression in human FDCs and induced migration of these cells. Normal human germinal centers expressed of MMP3, and MMP3 in the FDCs are increased by TNFα. The induction of MMP3 in FDCs is dependent on ERK1/2 activation. TNFα stimulation induced the promoter activity of the AP-1 binding sites in Mmp3 proximal promoter region. The induced expression of MMP3 increased FDC migration and the reduction of MMP3 expression decreased FDC migration. Overall, we identified a novel mechanism for the expression of MMP3 in FDCs to modulate the migration, a process of lymphoid follicle development. Lymphoid follicles are observed in the lesion of many autoimmune and autoantibody-associated diseases, thereby control of TNFα-mediated migration of FDCs may suppress those diseases.