Ectopic lymphoid-like structures in infection, cancer and autoimmunity

Pitzalis, Costantino; Jones, Gareth Wyn; Bombardieri, Michèle; Jones, Simon A.

doi:10.1038/nri3700

Cited by 532 publications

(590 citation statements)

References 188 publications

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“…In humans, ectopic lymphoid structures often develop at sites of inflammation caused by infection, cancer, and autoimmunity (52). However, the induction and pathological nature of ectopic lymphoid structures in chronic allergic diseases was largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Thy1⁺IL-7⁺lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

Shinoda

Hirahara

Iinuma

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Memory CD4 + T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT) are formed during chronic allergic inflammation in the lung, and that memory-type pathogenic Th2 (Tpath2) cells capable of driving allergic inflammation are maintained within the iBALT structures. The maintenance of memory Th2 cells within iBALT is supported by Thy1 + IL-7-producing lymphatic endothelial cells (LECs). The Thy1 + IL-7-producing LECs express IL-33 and T-cell-attracting chemokines CCL21 and CCL19. Moreover, ectopic lymphoid structures consisting of memory CD4 + T cells and IL-7 + IL-33 + LECs were found in nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, Thy1 + IL-7-producing LECs control chronic allergic airway inflammation by providing a survival niche for memory-type Tpath2 cells.

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Section: Discussionmentioning

confidence: 99%

Thy1⁺IL-7⁺lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

Shinoda

Hirahara

Iinuma

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…However, there is emerging appreciation that during chronic inflammation, infiltrating immune cells can form highly organized aggregates of lymphoid cells that resemble SLOs. These ectopic lymphoid follicles (ELFs), also known as tertiary lymphoid structures, can propagate local antigen‐specific responses within tissues 9, 10. Occasionally, these ELFs are named according to their site of development (e.g.…”

Section: Secondary and Ectopic Lymphoid Organsmentioning

confidence: 99%

“…The expression of homeostatic chemokines is increased in tissues where ELFs have emerged in response to foreign or auto antigens 1, 9, 10, 12. Chemokines such as CXCL13, CCL19, CCL21 and CXCL12 are involved not only in the initiation of ELF development, but also in the maintenance of the highly organized cellular architecture of established ELFs and SLOs.…”

Section: Homeostatic Chemokines In Elf Developmentmentioning

confidence: 99%

“…Ectopic lymphoid follicles are associated with various autoimmune and chronic inflammatory diseases including rheumatoid arthritis,11, 101, 102 Sjögren syndrome,103 multiple sclerosis,104 experimental diabetes,105 atherosclerosis,106, 107 inflammatory bowel disease108, 109 and chronic obstructive pulmonary disease110, 111 (for a comprehensive review of ELFs in autoimmunity see refs 10, 76). In contrast to their roles in infection and cancer, ELFs in chronic inflammatory diseases are primarily associated with disease exacerbation.…”

Section: Elfs As Perpetuators Of Inflammation‐driven Pathologymentioning

confidence: 99%

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Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

2015

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SummaryLymphoid neogenesis is traditionally viewed as a pre‐programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in lymph nodes and spleen into discrete structures regulates antigen‐specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto‐immunity, transplantation, cancer or environmental irritants. Although these structures affect local immune responses, the contribution of these lymphoid aggregates to the underlining pathology are highly context dependent and can elicit either protective or deleterious outcomes. Here we review the cellular and molecular mechanisms responsible for ectopic lymphoid neogenesis and consider the relevance of these structures in human disease.

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“…In most cancers, TLS are associated with a favorable prognosis [15][16][17]. It must be noted that TLS are also speculated to be a mere bystander effect of inflammation within the TME and not as an active participant in mediating anti-tumour immune response in certain cancer sites [12,18]. Interestingly, a recent study on hepatocellular carcinoma describes these TLS as micro niches supporting tumour cell growth and survival [19].…”

Section: Introductionmentioning

confidence: 99%

Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer

Koti¹,

Xu²,

Ren³

et al. 2018

BLC

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Abstract.Background: Urothelial bladder cancer (UBC) is a highly prevalent disease in North America, however its optimal management remains elusive. The contribution of B cell associated responses is poorly understood in bladder cancer. Lymphoid neogenesis is a hallmark of an active immune response at tumor sites that sometimes leads to formation of tertiary lymphoid structures (TLS) that resemble germinal centers formed in secondary lymphoid organs. Objective: This study was conducted with an aim to investigate the presence and characteristics of TLS in UBC with a focus to compare and contrast the TLS formation in treatment naive low grade non-muscle invasive (NMIBC) and muscle invasive bladder cancers (MIBC). Methods: The study cohort consisted of transurethral bladder resection tumour (TURBT) specimens from 28 patients. Sections showing lymphoid aggregates in hematoxylin and eosin (H&E) stained TURBT specimens were further subjected to multi-color immunohistochemistry using immune cell markers specific to CD20 + B cells, CD3 + and CD8 + T cells, PNAd + high endothelial venules, CD208 + mature dendritic cells, CD21 + follicular dendritic cells to confirm the hallmarks of classical germinal centers. Results: Our pilot study investigating the presence of TLS in bladder cancer patients is the first to demonstrate that well-formed TLS are more common in aggressive high grade MIBC tumors compared to low grade NIMBC. Conclusions: These novel findings suggest B cell mediated anti-tumour humoral immune responses in bladder cancer progression.

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Ectopic lymphoid-like structures in infection, cancer and autoimmunity

Cited by 532 publications

References 188 publications

Thy1⁺IL-7⁺lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

Thy1⁺IL-7⁺lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer

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Ectopic lymphoid-like structures in infection, cancer and autoimmunity

Cited by 532 publications

References 188 publications

Thy1+IL-7+lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

Thy1+IL-7+lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer

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Thy1⁺IL-7⁺lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

Thy1⁺IL-7⁺lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation