title: Human Lymph Node-Derived Fibroblastic and Double-Negative Reticular Cells Alter Their Chemokines and Cytokines Expression Profile Following Inflammatory Stimuli.
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.
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Severino
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, São Paulo, Brazil; Programa de Alergia e Imunopatologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: Diana Torres
authors.initials: DT
authors.lastname: Palomino
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, São Paulo, Brazil; Programa de Alergia e Imunopatologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: Heliene
authors.initials: H
authors.lastname: Alvarenga
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Camila Bononi
authors.initials: CB
authors.lastname: Almeida
authors.affiliation: Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Denise Cunha
authors.initials: DC
authors.lastname: Pasqualim
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, Brazil; Endocrinology Department, Santa Casa de Misericórdia de Sao Paulo, São Paulo, Brazil.
authors.forename: Adriano
authors.initials: A
authors.lastname: Cury
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, São Paulo, Brazil; Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Paolo Rogério
authors.initials: PR
authors.lastname: Salvalaggio
authors.affiliation: Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Antonio Luiz
authors.initials: AL
authors.lastname: De Vasconcelos Macedo
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Maria Claudina
authors.initials: MC
authors.lastname: Andrade
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Aloia
authors.affiliation: Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bromberg
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Luiz Vicente
authors.initials: LV
authors.lastname: Rizzo
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Fernanda Agostini
authors.initials: FA
authors.lastname: Rocha
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein , São Paulo , Brazil.
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Marti
keywords: chemokines; double-negative cells; fibroblastic reticular cell; human lymph nodes; podoplanin