title: Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic Inflammation.
abstract: Tertiary lymphoid structures (TLS) are organized aggregates of lymphocytes, myeloid, and stromal cells that provide ectopic hubs for acquired immune responses. TLS share phenotypical and functional features with secondary lymphoid organs (SLO); however, they require persistent inflammatory signals to arise and are often observed at target sites of autoimmune disease, chronic infection, cancer, and organ transplantation. Over the past 10 years, important progress has been made in our understanding of the role of stromal fibroblasts in SLO development, organization, and function. A complex and stereotyped series of events regulate fibroblast differentiation from embryonic life in SLOs to lymphoid organ architecture observed in adults. In contrast, TLS-associated fibroblasts differentiate from postnatal, locally activated mesenchyme, predominantly in settings of inflammation and persistent antigen presentation. Therefore, there are critical differences in the cellular and molecular requirements that regulate SLO versus TLS development that ultimately impact on stromal and hematopoietic cell function. These differences may contribute to the pathogenic nature of TLS in the context of chronic inflammation and malignant transformation and offer a window of opportunity for therapeutic interventions in TLS associated pathologies.
authors.affiliation: Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham , Birmingham , UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Barone
authors.affiliation: Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham , Birmingham , UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Gardner
authors.affiliation: Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham , Birmingham , UK.
authors.forename: Saba
authors.initials: S
authors.lastname: Nayar
authors.affiliation: Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham , Birmingham , UK.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Steinthal
authors.affiliation: Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham , Birmingham , UK.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection, University of Lausanne , Lausanne , Switzerland.
authors.forename: Sanjiv A
authors.initials: SA
authors.lastname: Luther
keywords: beta2 heterotrimer; chemokines; fibroblasts; lymphotoxin alpha1; tertiary lymphoid structures; tumor necrosis factor-alpha