The lymph node stromal laminin α5 shapes alloimmunity

Li, Lushen; Shirkey, Marina W.; Zhang, Tianshu; Xiong, Yanbao; Piao, Wenji; Saxena, Vikas; Paluskievicz, Christina; Lee, Young S.; Toney, Nicholas; Cerel, Benjamin M.; Li, Qinshan; Thézenas, Simon; Smith, Kyle D.; Hippen, Keli L.; Blazar, Bruce R.; Abdi, Reza; Bromberg, Jonathan S.

doi:10.1172/jci135099

Cited by 28 publications

(43 citation statements)

References 58 publications

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“…As unveiled in murine models, IL-33 is primarily secreted by TRCs and MedRCs [ 44 ] and sustains Tregs, group 2 innate lymphoid cells (ILC2s), and macrophages [ 45 – 47 ], but suppresses proinflammatory type 1 T helper (Th1) cells [ 48 ]. Relative to WT littermates, Pdgfrβ-Cre +/− × Laminin α5 fl/fl mice lacking laminin α5 in LN FRCs harbor increased numbers of Tregs in the T-zone [ 49 ] overlapping with an IL-33-rich area [ 44 ], suggesting that IL-33 might contribute to a pro-tolerant LN niche by supporting Tregs. Overall, by producing functional molecules, presenting autoantigens, and secreting cytokines, FRCs can support pro-tolerant immune cells and constrain proinflammatory cells, thereby contributing to immune homeostasis and self-tolerance.…”

Section: Frc Functions During Immune Responsesmentioning

confidence: 99%

“…As a result, treating the recipients with one dose of anti-CD40L mAb (i.v.) dramatically enhanced murine cardiac transplantation tolerance relative to controls [ 49 ].…”

Section: Frcs In Tolerancementioning

confidence: 99%

“…During Th17 differentiation, T cells recognized laminin α5 via the receptor α-dystroglycan (DG) [ 60 ]. Depletion of LN FRC laminin α5 in Pdgfrβ-Cre +/− × Laminin α5 fl/fl mice increased HEV size and number and increased Treg numbers in the T-zone relative to Cre-negative littermates [ 49 ]. Moreover, depletion of FRC laminin α5 in this study also improved murine cardiac allograft survival [ 49 ].…”

Section: Frcs In Tolerancementioning

confidence: 99%

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Lymph node fibroblastic reticular cells steer immune responses

Abdi

et al. 2021

Trends in Immunology

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Lymph nodes (LNs), where immune responses are initiated, are organized into distinctive compartments by fibroblastic reticular cells (FRCs). FRCs imprint immune responses by supporting LN architecture, recruiting immune cells, coordinating immune cell crosstalk, and presenting antigens. Recent high-resolution transcriptional and histological analyses have enriched our knowledge of LN FRC genetic and spatial heterogeneities. Here, we summarize updated anatomic, phenotypic, and functional identities of FRC subsets, delve into topological and transcriptional remodeling of FRCs in inflammation, and illustrate the crosstalk between FRCs and immune cells. Discussing FRC functions in immunity and tolerance, we highlight state-of-the-art FRC-based therapeutic approaches for maintaining physiological homeostasis, steering protective immunity, inducing transplantation tolerance, and treating diverse immune-related diseases.

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Section: Frc Functions During Immune Responsesmentioning

confidence: 99%

“…As a result, treating the recipients with one dose of anti-CD40L mAb (i.v.) dramatically enhanced murine cardiac transplantation tolerance relative to controls [ 49 ].…”

Section: Frcs In Tolerancementioning

confidence: 99%

Section: Frcs In Tolerancementioning

confidence: 99%

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Lymph node fibroblastic reticular cells steer immune responses

Abdi

et al. 2021

Trends in Immunology

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Section: Lnscs Modulate Alloreactive T Cell Activation Following Tmentioning

confidence: 99%

“…Recent studies have revealed important roles of FRCs in the modulation of alloreactive T cells after cardiac transplantation in mice [ 76 , 77 ]. By producing the extracellular matrix (ECM) inflammatory component Laminin α5 (Lama5), FRCs surrounding the HEVs in the paracortical zone of LNs promote alloreactive T cell activation, leading to graft rejection ( Figure 2 A) [ 76 ]. Genetic abolition of Lama5 expression in SCs results in increased Treg numbers in LNs, providing a tolerogenic environment associated with decreased alloreactive T cell activation and enhanced cardiac allograft acceptance [ 76 ].…”

Section: Lnscs Modulate Alloreactive T Cell Activation Following Tmentioning

confidence: 99%

Lymph Node Stromal Cells: Mapmakers of T Cell Immunity

Harlé

Kowalski

Garnier

et al. 2020

IJMS

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Stromal cells (SCs) are strategically positioned in both lymphoid and nonlymphoid organs to provide a scaffold and orchestrate immunity by modulating immune cell maturation, migration and activation. Recent characterizations of SCs have expanded our understanding of their heterogeneity and suggested a functional specialization of distinct SC subsets, further modulated by the microenvironment. Lymph node SCs (LNSCs) have been shown to be particularly important in maintaining immune homeostasis and T cell tolerance. Under inflammation situations, such as viral infections or tumor development, SCs undergo profound changes in their numbers and phenotype and play important roles in contributing to either the activation or the control of T cell immunity. In this review, we highlight the role of SCs located in LNs in shaping peripheral T cell responses in different immune contexts, such as autoimmunity, viral and cancer immunity.

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The aging of the immune system and its implications for transplantation

et al. 2023

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By the last third of life, most mammals, including humans, exhibit a decline in immune cell numbers, immune organ structure, and immune defense of the organism, commonly known as immunosenescence. This decline leads to clinical manifestations of increased susceptibility to infections, particularly those caused by emerging and reemerging microorganisms, which can reach staggering levels—infection with SARS-CoV-2 has been 270-fold more lethal to older adults over 80 years of age, compared to their 18–39-year-old counterparts. However, while this would be expected to be beneficial to situations where hyporeactivity of the immune system may be desirable, this is not always the case. Here, we discuss the cellular and molecular underpinnings of immunosenescence as they pertain to outcomes of solid organ and hematopoietic transplantation.

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The lymph node stromal laminin α5 shapes alloimmunity

Cited by 28 publications

References 58 publications

Lymph node fibroblastic reticular cells steer immune responses

Lymph node fibroblastic reticular cells steer immune responses

Lymph Node Stromal Cells: Mapmakers of T Cell Immunity

The aging of the immune system and its implications for transplantation

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