Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Maarouf, Omar H.; Uehara, Mayuko; Kasinath, Vivek; Solhjou, Zhabiz; Banouni, Naima; Bahmani, Baharak; Jiang, Liwei; Yilmam, Osman A.; Guleria, Indira; Lovitch, Scott B.; Grogan, Jane L.; Fiorina, Paolo; Sage, Peter T.; Bromberg, Jonathan S.; McGrath, Martina M.; Abdi, Reza

doi:10.1172/jci.insight.120546

Cited by 31 publications

(71 citation statements)

References 76 publications

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“…34 The immunosuppressive phenotype of FRCs is especially important toward the late phase of an immune response, in which the LN must involute to its steady-state functioning and microarchitecture to maintain immunological homeostasis and avoid sustained deleterious inflammation. 9 The LTβR-Ig-treated group suffered more severe kidney damage in comparison with an isotype control-treated group. 9 Chronic treatment with LTβR-Ig, a decoy fusion protein that blocks the actions of both ligands for LTβR (LTα1β2 and LIGHT), was associated with fibrosis in the dLNs of the mice that underwent IRI of the kidney, as demonstrated by increased fibronectin produced by FRCs.…”

Section: Fibroblastic Reticular Cell and Immunitymentioning

confidence: 96%

“…33 Infection with herpes simplex virus-1 (HSV-1) is associated with activation of the type-1 interferon (IFN) pathway in FRCs. 9 Chronic treatment with LTβR-Ig, a decoy fusion protein that blocks the actions of both ligands for LTβR (LTα1β2 and LIGHT), was associated with fibrosis in the dLNs of the mice that underwent IRI of the kidney, as demonstrated by increased fibronectin produced by FRCs. 27 A recent study suggested the integral role LTβR signaling plays in the switch of FRCs to an anti-inflammatory phenotype.…”

Section: Fibroblastic Reticular Cell and Immunitymentioning

confidence: 99%

“…27 A recent study suggested the integral role LTβR signaling plays in the switch of FRCs to an anti-inflammatory phenotype. 9 Thus, FRC-mediated fibrosis within the LN is associated with chronic injury to the organ it drains, suggesting that immunological crosstalk lingers between these two domains long after the initial insult has passed. 9 The LTβR-Ig-treated group suffered more severe kidney damage in comparison with an isotype control-treated group.…”

Section: Fibroblastic Reticular Cell and Immunitymentioning

confidence: 99%

“…3 For example, immature DCs (iDCs) express low levels of costimulatory molecules, major histocompatibility complexes (MHC) I and II, and pro-inflammatory cytokines. 9 These include loss of segregation of T and B cell zones, decreased proliferation of FRC, and fibrosis with deposition of type I collagen, fibronectin, and α smooth muscle actin. 4 The tumor draining LNs (dLNs) establish a site of dominant tumor tolerance through generation of iTreg, which prevents the activation and expansion of the incoming naïve tumor-specific T cells.…”

Section: Introductionmentioning

confidence: 99%

“…These iDC can limit effector T function and promote peripherally induced T regulatory cells (iTreg) differentiation in peripheral locations. 9 Chronic infection with human immunodeficiency virus (HIV) is characterized by the exhaustion of T cells which is in part a result of depletion of FRC and FRC-derived IL-7 T cell survival factor, resulting in T cell apoptosis. 5 Thymic-derived natural Treg (nTreg) can migrate to the LN and implement mechanisms of suppression ultimately achieving tolerance.…”

Section: Introductionmentioning

confidence: 99%

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Role of lymph node stroma and microenvironment in T cell tolerance

Saxena

Paluskievicz

et al. 2019

Immunological Reviews

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Lymph nodes (LNs) are at the cross roads of immunity and tolerance. These tissues are compartmentalized into specialized niche areas by lymph node stromal cells (LN SCs). LN SCs shape the LN microenvironment and guide immunological cells into different zones through establishment of a CCL19 and CCL21 gradient. Following local immunological cues, LN SCs modulate activity to support immune cell priming, activation, and fate. This review will present our current understanding of LN SC subsets roles in regulating T cell tolerance. Three major types of LN SC subsets, namely fibroblastic reticular cells, lymphatic endothelial cells, and blood endothelial cells, are discussed. These subsets serve as scaffolds to support and regulate T cell homeostasis. They contribute to tolerance by presenting peripheral tissue antigens to both CD4 and CD8 T cells. The role of LN SCs in regulating T cell migration and tolerance induction is discussed. Looking forward, recent advances in bioengineered materials and approaches to leverage LN SCs to induce T cell tolerance are highlighted, as are current clinical practices that allow for manipulation of the LN microenvironment to induce tolerance. Increased understanding of LN architecture, how different LN SCs integrate immunological cues and shape immune responses, and approaches to induce T cell tolerance will help further combat autoimmune diseases and graft rejection.

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Section: Fibroblastic Reticular Cell and Immunitymentioning

confidence: 96%

Section: Fibroblastic Reticular Cell and Immunitymentioning

confidence: 99%

Section: Fibroblastic Reticular Cell and Immunitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of lymph node stroma and microenvironment in T cell tolerance

Saxena

Paluskievicz

et al. 2019

Immunological Reviews

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Skin matrix meets immunomatrix—Implications for genetic and acquired diseases

Nyström,

Conradt,

Lehr

et al. 2024

JEADV Clinical Practice

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An extracellular matrix (ECM) is essential for multicellular life. Apart from being a scaffold, it is an actively signalling unit, orchestrating homo‐ and heterocellular communication to uphold tissue homeostasis or elicit an appropriate regenerative response after injury. The skin as a barrier organ meeting unremittent physical biological and chemical challenges is dependent on both a specialized ECM and attentive yet balanced immune surveillance. Intriguingly, skin‐like ECM composites occur in primary and secondary lymphoid organs. Evolutionary, the expansion of the ECM coincides with development of adaptive immunity. Studies of acquired and genetic skin diseases suggest that the skin and lymphoid ECMs are essential, emerging, but yet‐under‐appreciated, gatekeepers of dermal immune homeostasis. Here, we summarize knowledge of the dermal and skin‐distal lymphoid ECM as a mediator of skin immune homeostasis. We argue that increased awareness of the lymphoid‐ECM as a potential regulator of skin immunity will increase our understanding of diseases linked to skin inflammation and allow for improved treatment options of them.

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The Biophysics of Lymphatic Transport: Engineering Tools and Immunological Consequences

2019

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Lymphatic vessels mediate fluid flows that affect antigen distribution and delivery, lymph node stromal remodeling, and cell-cell interactions, to thus regulate immune activation. Here we review the functional role of lymphatic transport and lymph node biomechanics in immunity. We present experimental tools that enable quantitative analysis of lymphatic transport and lymph node dynamics in vitro and in vivo. Finally, we discuss the current understanding for how changes in lymphatic transport and lymph node biomechanics contribute to pathogenesis of conditions including cancer, aging, neurodegeneration, and infection.

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Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Cited by 31 publications

References 76 publications

Role of lymph node stroma and microenvironment in T cell tolerance

Role of lymph node stroma and microenvironment in T cell tolerance

Skin matrix meets immunomatrix—Implications for genetic and acquired diseases

The Biophysics of Lymphatic Transport: Engineering Tools and Immunological Consequences

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