The Migration of Human Follicular Dendritic Cell-Like Cell Is Facilitated by Matrix Metalloproteinase 3 Expression That Is Mediated through TNFα-ERK1/2-AP1 Signaling.

Hyo-Kyung Pak,Jin Roh,Chaohong Liu,Yong-Woo Kim,Yoo-Sam Chung,Chan-Sik Park,Bora Nam,Minchan Gil,A-Neum Lee,Samanta Taurone

doi:10.1155/2021/8483938

Abstract

Follicular dendritic cells are important stromal components of the germinal center (GC) and have pivotal roles in maintaining the GC microenvironment for high-affinity antibody production. Tumor necrosis factor-α (TNFα) is essential for the development and functions of follicular dendritic cells. Despite the importance of follicular dendritic cells in humoral immunity, their molecular control mechanisms have yet to be fully elucidated due to the lack of an adequate investigation system. Here, we have used a unique human primary follicular dendritic cell-like cell (FDCLC) to demonstrate that the migration of these cells is enhanced by TNFα-mediated metalloproteinase 3 (MMP3) expression. MMP3 was found to be highly expressed in normal human GCs and markedly upregulated in human primary FDCLCs by TNFα. TNFα induced ERK1/2 phosphorylation and the transcription of MMP3 through AP1. TNFα treatment increased FDCLC migration, and a knockdown of MMP3 significantly reduced the TNFα-induced migration of FDCLCs. Overall, we have newly identified a control mechanism for the expression of MMP3 in FDCLCs that modulates their migration and may indicate an important role in GC biology. Since GCs are observed in the lesions of autoimmune diseases and lymphomas, targeting the MMP3/TNFα-mediated migration of stromal cells in the B cell follicle may have great potential as a future therapeutic modality against aberrant GC-associated disorders.

Highlights

The germinal center (GC) is critical for the production of high-affinity protective antibodies and plays an important role in various immunologic disorders including autoimmune diseases and lymphomas [1, 2]
Because the matrix metalloproteinases (MMPs) are indispensable for cell migration and tissue remodeling, we focused on their specific roles in follicular dendritic cell-like cell (FDCLC)
We found that MMP3 siRNAtransfected (MMP3i) FDCLC had reduced the length of dendrites by 34% on collagen-1-coated plates compared to Scr cells (Figures 3(e) and 3(f))

Summary

Introduction

The germinal center (GC) is critical for the production of high-affinity protective antibodies and plays an important role in various immunologic disorders including autoimmune diseases and lymphomas [1, 2]. Follicular dendritic cells (FDCs) are the major stromal components of GCs and are essential for their formation and maintenance. These cells form network-like structures with their long dendrites and provide crucial survival and differentiation signals to GC-B cells [3, 4]. The spreading of the GCs together with FDCs is one of the important pathologic features of lymphoid diseases such as rheumatoid arthritis and follicular lymphomas [6]. Many of the molecular mechanisms underlying the actions of FDCs remain to be identified because of the lack of adequate investigation systems for these cells, in relation to their migration

Methods

Results

Conclusion