Fibroblastic Reticular Cells: Organization and Regulation of the T Lymphocyte Life Cycle

Brown, Flavian D.; Turley, Shannon J.

doi:10.4049/jimmunol.1402520

Cited by 112 publications

(96 citation statements)

References 70 publications

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“…Fibroblastic reticular cell subsets, including FDC, are defined by their phenotype, anatomical location, and function (2, 24, 153, 154) (Figure 2). T zone FRCs or TRC classically inhabit the T cell cortex in LNs and are characterized by the expression of podoplanin and lack of the vascular marker CD31.…”

Section: Stromal Fibroblast Organization In Slos and Tlssmentioning

confidence: 99%

Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic Inflammation

et al. 2016

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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.

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Section: Stromal Fibroblast Organization In Slos and Tlssmentioning

confidence: 99%

Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic Inflammation

et al. 2016

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“…Lymph node architecture and adaptive immune responses are also modulated by changes within the FRC network during infection (20, 58). Histologic examination of FRC networks within MLN sections from WT, STING −/− , and CD118 −/− mice was achieved using a classical silver stain technique to identify reticulin fibers (Fig.…”

Section: Resultsmentioning

confidence: 99%

Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in Mice Lacking the STING-IFNα/β Defense Pathways

Royer

Conrady

Carr

2016

The Journal of Immunology

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Type I interferon (IFNα/β)-driven immune responses to acute viral infection are critical to counter replication and prevent dissemination. However, the mechanisms underlying host resistance to herpes simplex virus type 1 (HSV-1) are incompletely understood. Here we show that mice with deficiencies in IFNα/β signaling or STING exhibit exacerbated neurovirulence and atypical lymphotropic dissemination of HSV-1 following ocular infection. Synergy between IFNα/β signaling and efficacy of early adaptive immune responses to HSV-1 were dissected using bone marrow chimeras and adoptive cell transfer approaches to profile clonal expansion, effector function, and recruitment of HSV-specific CD8+ T cells. Lymphotropic viral dissemination was commensurate with abrogated CD8+ T cell responses and pathological alterations of fibroblastic reticular cell (FRC) networks in the draining lymph nodes. Our results show that resistance to HSV-1 in the TG during acute infection is conferred in part by STING and IFNα/β-signaling in both bone marrow-derived and resident cells, which coalesce to support a robust HSV-1-specific CD8+ T cell response.

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“…However, in addition to being sites in which immune responses are initiated, secondary lymphoid organs are also sites that foster immune privilege that prevents autoimmunity by inducing tolerance and deleting autoreactive T cells, suppressing effector T cell proliferation, and supporting regulatory T cells (Fletcher et al, 2011, 2014, 2015; Brown and Turley, 2015). Currently, lymph node fibroblasts are being explored for their therapeutic potential to circumvent unwanted inflammation in autoimmune diseases, sepsis, and graft rejection after organ transplantation (Fletcher et al, 2011, 2014, 2015).…”

Section: Possible Mechanisms By Which Cafs Contribute To Inverse Survmentioning

confidence: 99%

A Paradoxical Correlation of Cancer-Associated Fibroblasts With Survival Outcomes in B-Cell Lymphomas and Carcinomas

Haro

Oršulić

2018

Front. Cell Dev. Biol.

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The tumor microenvironment is increasingly recognized as an active participant in tumor progression. A recent pan-cancer genomic profile analysis has revealed that gene signatures representing components of the tumor microenvironment are robust predictors of survival. A stromal gene signature representing fibroblasts and extracellular matrix components has been associated with good survival in diffuse large B-cell lymphoma (DLBCL). Paradoxically, a closely related gene signature has been shown to correlate with poor survival in carcinomas, including breast, ovarian, pancreatic, and colorectal cancer. To date, there has been no explanation for this paradoxical inverse correlation with survival outcomes in DLBCL and carcinomas. Using public gene data sets, we confirm that the DLBCL stromal gene signature is associated with good survival in DLBCL and several other B-cell lymphomas while it is associated with poor survival in ovarian cancer and several other solid tumors. We show that the DLBCL stromal gene signature is enriched in lymphoid fibroblasts in normal lymph nodes and in cancer-associated fibroblasts (CAFs) in ovarian cancer. Based on these findings, we propose several possible mechanisms by which CAFs may contribute to opposite survival outcomes in B-cell lymphomas and carcinomas.

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Fibroblastic Reticular Cells: Organization and Regulation of the T Lymphocyte Life Cycle

Cited by 112 publications

References 70 publications

Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic Inflammation

Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic Inflammation

Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in Mice Lacking the STING-IFNα/β Defense Pathways

A Paradoxical Correlation of Cancer-Associated Fibroblasts With Survival Outcomes in B-Cell Lymphomas and Carcinomas

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