Human Lymph Node-Derived Fibroblastic and Double-Negative Reticular Cells Alter Their Chemokines and Cytokines Expression Profile Following Inflammatory Stimuli

Patricia Severino,Maria Claudina Andrade,Antonio Luiz De Vasconcelos Macedo,Camila Bononi Almeida,Adriano Cury,Thiago Aloia,Silvio Bromberg,Fernanda Agostini Rocha,Paolo Rogério Salvalaggio,Luiz Vicente Rizzo,Denise Cunha Pasqualim,Heliene Alvarenga,Diana Torres Palomino,Luciana C Marti

doi:10.3389/fimmu.2017.00141

Abstract

Lymph node (LN) is a secondary lymphoid organ with highly organized and compartmentalized structure. LNs harbor B, T, and other cells among fibroblastic reticular cells (FRCs). FRCs are characterized by both podoplanin (PDPN/gp38) expression and by the lack of CD31 expression. FRCs are involved in several immune response processes but mechanisms underlying their function are still under investigation. Double-negative cells (DNCs), another cell population within LNs, are even less understood. They do not express PDPN or CD31, their localization within the LN is unknown, and their phenotype and function remain to be elucidated. This study evaluates the gene expression and cytokines and chemokines profile of human LN-derived FRCs and DNCs during homeostasis and following inflammatory stimuli. Cytokines and chemokines secreted by human FRCs and DNCs partially diverged from those identified in murine models that used similar stimulation. Cytokine and chemokine secretion and their receptors expression levels differed between stimulated DNCs and FRCs, with FRCs expressing a broader range of chemokines. Additionally, dendritic cells demonstrated increased migration toward FRCs, possibly due to chemokine-induced chemotaxis since migration was significantly decreased upon neutralization of secreted CCL2 and CCL20. Our study contributes to the understanding of the biology and functions of FRCs and DNCs and, accordingly, of the mechanisms involving them in immune cells activation and migration.

Highlights

The immunological function of lymph nodes (LNs) includes the initiation of antigen-specific immune responses as well as the induction of tolerance when required
We demonstrate that, following inflammatory stimulation, the secretion of interleukins and chemokines by human LN-derived fibroblastic reticular cells (FRCs) and Double-negative cells (DNCs) partially differed from those identified in murine models
LNs were evaluated for cells distribution using histochemistry markers for CD3, CD20, and CD68 [24] and, we observed that T lymphocytes were present in the paracortex region, B lymphocytes were within the follicles, and the macrophages were distributed throughout the LN

Summary

Introduction

The immunological function of lymph nodes (LNs) includes the initiation of antigen-specific immune responses as well as the induction of tolerance when required. These secondary lymphoid organs possess a structured morphology and harbor a variety of cell populations, including lymphocytes B, T, and other less characterized cell populations. The fibroblastic reticular cells (FRCs) are phenotypically characterized by both podoplanin expression (PDPN, gp38) and by the absence of CD31 expression [1,2,3]. FRCs are known to participate in several immune response processes, including immune cells homing and activation, but essential mechanisms fundamental to these functions are still under investigation [2, 4]. These cells do not express gp or CD31, their localization within LNs is unclear, and their function remains to be elucidated [5,6,7]

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Results

Conclusion