Gliadin-reactive vitamin D-sensitive proinflammatory ILCPs are enriched in celiac patients

Ercolano, Giuseppe; Moretti, Alex; Falquet, Maryline; Wyss, Tania; Tran, Ngoc Lan; Senoner, Isis; Marinoni, Maddalena; Agosti, Massimo; Salvatore, Silvia; Jandus, Camilla; Trabanelli, Sara

doi:10.1016/j.celrep.2022.110956

Cited by 8 publications

(7 citation statements)

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“…Multisystem CD is characterized by circulating innate lymphoid cells and increased levels of IL-18, IFN-γ, and innate lymphoid cell precursors were noted ( 3 ). A reduced vitamin D level has been reported to be correlated with higher IFN-γ and innate lymphoid cell precursor ( 4 ). Vitamin D deficiency is shown to induce T-cell-mediated pro-inflammatory immune responses that are pivotal in CD ( 30 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

“…Vitamin D deficiency is shown to induce T-cell-mediated pro-inflammatory immune responses that are pivotal in CD ( 30 , 31 ). This gave an insight into dietary supplementation of vitamin D as a therapeutic approach to inhibit cytokine IFN-γ production ( 4 ). Several cross-section studies concluded the association of vitamin D deficiency with immune-related diseases ( 32 – 34 ).…”

Section: Discussionmentioning

confidence: 99%

“…Though the etiology of CD is not well understood but is marked by the presence of inflammatory cytokines IL18, IL17, TNF-α, IL12, IL21, and IL15 ( 3 ). Vitamin D was found to be associated with reducing the effects of inflammatory molecules ( 4 ). Components of the immune system, such as B-lymphocytes, T-lymphocytes, and dendritic cells, are influenced by the regulatory effects of vitamin D and expressed vitamin D receptor (VDR), which is involved in the biological activity of 1,25(OH) 2 D3, and these cells also have the capability of locally synthesizing active 1,25(OH) 2 D3 ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

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A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease

2023

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PurposeAs an immune-modulator, vitamin D is known to regulate immune response and is implicated in disease pathogenesis. Celiac disease (CD) is a systemic autoimmune disease and susceptibility conferred by vitamin D metabolism is under investigation. Studies on the association of vitamin D metabolism and genetic polymorphisms are expected to explain CD pathogenesis. We performed a systematic review–based meta-analysis to investigate the 25(OH)D serum levels and susceptibility conferred by the genetic variants of VDR in CD.MethodsSystematic review was conducted through a web-based literature search following stringent study inclusion–exclusion criteria. The Newcastle–Ottawa Scale and GRADE tools were used to assess the quality of evidence in studies and the study outcome. Cohen's κ value was estimated to access the reviewer's agreement. RevMan 5.4.1 was used to perform the meta-analyses. Weighted mean difference and Meta p-value was assessed for 25(OH)D serum levels. Meta-odds ratio and Z-test p-value were evaluated to estimate the allelic susceptibility of VDR variants.ResultsA total of 8 out of 12 studies were evaluated for “25(OH)D” serum level, while four studies were found eligible for SNPs (Bsm1, Apa1, Fok1, and Taq1) of VDR. Significantly higher levels [WMD = 5.49, p < 0.00001] of 25(OH)D were observed in healthy controls than in patients with CD. rs2228570-T (Fok1) [Meta-OR = 1.52, p = 0.02] was confirmed to be predisposing allele for CD.ConclusionReduced serum level of 25(OH)D and association of Fok1 T-allele of VDR confirmed in this study plays a critical role in immunomodulation and maintaining barrier integrity, which is majorly implicated in CD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease

2023

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“…Three different subsets of helper ILCs, namely ILC1s, ILC2s and ILC3s, can be distinguished based on transcriptional regulators and cytokine secretion, which functionally mirror helper CD4 + T cells (i.e., Th1, Th2 and Th17, respectively) [4][5][6] . ILC3s are poorly represented in PB, where they are comprised in a cKit + population of ILC precursors (ILCPs) 7,8 . ILCs have been shown to be involved in different biological processes, both physiological, such as antimicrobial responses, tissue homeostasis, lymphoid organ development, and pathological, such as autoimmunity and cancer 9 .…”

Section: Introductionmentioning

confidence: 99%

“… 4–6 ILC3 are poorly represented in PB, where they are comprised in a cKit + population of ILC precursors (ILCP). 7 , 8 ILC have been shown to be involved in different biological processes, both physiological, such as antimicrobial responses, tissue homeostasis, lymphoid organ development, and pathological, such as autoimmunity and cancer. 9 Previous evidence showed how ILC are phenotypically or functionally altered in several solid tumors and in hematologic malignancies.…”

Section: Introductionmentioning

confidence: 99%

IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia

Fiordi¹,

Salvestrini²,

Gugliotta³

et al. 2023

haematol

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Chronic Myeloid Leukemia (CML) is a hematologic malignancy associated to an unregulated growth of myeloid cells in Bone Marrow (BM) and Peripheral Blood (PB), characterized by the BCR-ABL1 translocation. Given the known cytokine impairment in the leukemic niche of CML, we investigated the impact of this microenvironmental dysregulation on Innate Lymphoid Cells (ILCs), whose role in cancer has recently emerged. Three ILC subsets are identified based on transcriptional profiles and cytokine secretion. We observed that IL-18 and VEGF-A are increased in CML patients’ sera and that ILC2s are enriched in CML PB and BM. We found that IL-18 drives ILC2 proliferation and that CML ILC2s highly express CXCR4 and CXCR7 BM-homing receptors, potentially explaining their enrichment in PB and BM, respectively. Next, we showed that ILC2s are hyper-activated through a tumor-derived VEGF-A-dependent mechanism, which leads to higher IL-13 secretion. In response to IL-13, leukemic cells increase their clonogenic capacity. Finally, we discovered that the pro-tumoral axis involving VEGF-A, IL-18 and ILC2s was disrupted upon Tyrosine Kinase Inhibitors’ (TKIs) treatment, normalizing the levels of all these players in CML patients responding to therapy. Overall, our study uncovers the involvement of ILC2s in CML progression, mediated by VEGF-A and IL-18.

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Vitamin D and systemic lupus erythematosus: Causality and association with disease activity and therapeutics

Ho,

Wu,

Luo

et al. 2024

Biochemical Pharmacology

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Gliadin-reactive vitamin D-sensitive proinflammatory ILCPs are enriched in celiac patients

Cited by 8 publications

References 67 publications

A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease

A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease

IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia

Vitamin D and systemic lupus erythematosus: Causality and association with disease activity and therapeutics

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