Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele

Al-Mossawi, Hussein; Yager, Nicole; Ca, Taylor; Lau, Evelyn; Danielli, Sara; Wit, Jelle de; Gilchrist, James J.; Nassiri, Isar; Mahé, Elise A.; Rizvi, Laila; Makino, Seiko; Cheeseman, Jane; Neville, Matt J.; Knight, Julian C.; Bowness, Paul; Fairfax, Benjamin P.

doi:10.1038/s41467-019-12393-1

Cited by 42 publications

(33 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Though IL7R had originally been reported to be essential exclusively for lymphocyte development and survival, a few recent studies, including ours, have found that it also plays roles in myeloid cell development [6][7][8] . Interestingly, in addition to our finding that IL7R regulates trMac specification during mouse fetal development 4 , studies in humans have reported that other myeloid cell types, including monocytes and eosinophils, may express IL7R 7,9 . Furthermore, these cells can upregulate IL7R mRNA and surface protein upon stimulation with lipopolysaccharide (LPS), a known activator of eosinophils.…”

Section: Introductionsupporting

confidence: 53%

“…Our data presented here reveal that IL7R is required for specific myeloid cell homeostasis in the lungs, PB, and BM of adult mice. Other groups have reported that human eosinophils have detectable levels of IL7Ra mRNA and surface protein 7,8 , and that IL7R mRNA can be induced in human monocytes with LPS stimulation 9 . Similarly, we previously found that trMacs in the lung and other tissues transiently express IL7Rα during development 6 .…”

Section: Il7r Deletion Caused Alterations In Cytokines Involved In Mymentioning

confidence: 97%

See 1 more Smart Citation

Interleukin 7 receptor (IL7R) is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells

Cool

Worthington

Poscablo

et al. 2020

Preprint

View full text Add to dashboard Cite

Respiratory diseases are a leading cause of death worldwide, with highly varied vulnerability to disease between individuals. The underlying reasons of disease susceptibility are unknown, but often include a variable immune response in lungs. Recently, we identified a surprising novel role of the interleukin 7 receptor (IL7R), a primarily lymphoid-associated regulator, in fetal-specified, lung-resident macrophage development. Here, we report that traditional, hematopoietic stem cell-derived myeloid cells in the adult lung, peripheral blood, and bone marrow also depend on IL7R expression. Using single and double germline knockout models, we found that eosinophil numbers were reduced upon deletion of IL7Rα. We then employed two Cre recombinase models in lineage tracing experiments to test whether these cells developed through an IL7Rα+ pathway. Despite the impact of IL7Rα deletion, IL7R-Cre labeled only a minimal fraction of eosinophils. We therefore examined the intrinsic versus extrinsic requirement for IL7R in the production of eosinophils using reciprocal hematopoietic stem cell transplantation assays. These assays revealed that extrinsic, but not eosinophil-intrinsic, IL7R is required for eosinophil reconstitution by HSCs in the adult lung. To determine which external factors may be influencing eosinophil development and survival, we performed a cytokine array analysis between wild-type and IL7Rα-deficient mice and found several differentially regulated proteins. These findings expand upon our previous publication that IL7R is required not only for proper lymphoid cell development and homeostasis, but also for myeloid cell homeostasis in tissues.HighlightsLoss of IL7Rα resulted in significantly fewer eosinophils in adult miceIL7R-Cre lineage tracing revealed minimal labeling of eosinophilsIL7Rα-deficient HSCs robustly reconstituted eosinophils in a WT hostWT HSCs failed to fully reconstitute eosinophils in IL7Rα-/- hostsSeveral cytokines are differentially expressed in WT and IL7Rα-deficient mice

show abstract

Section: Introductionsupporting

confidence: 53%

Section: Il7r Deletion Caused Alterations In Cytokines Involved In Mymentioning

confidence: 97%

Interleukin 7 receptor (IL7R) is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells

Cool

Worthington

Poscablo

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…On the other hand, a highlighted biological process detected in the CCB breed was the negative regulation of T-cellmediated cytotoxicity, associated with IL7R gene. In humans, variations in this gene have been linked with autoimmune risk (Al-Mossawi et al, 2019), while in livestock animals, it has been described to be associated with growth traits (Jia et al, 2019;Zhu et al, 2019), which corroborates the purpose of this breed formation as a beef cattle.…”

Section: Discussionmentioning

confidence: 80%

Genome-Wide Analyses Reveal the Genetic Architecture and Candidate Genes of Indicine, Taurine, Synthetic Crossbreds, and Locally Adapted Cattle in Brazil

Verardo

Silva

Machado³

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

Cattle population history, breeding systems, and geographic subdivision may be reflected in runs of homozygosity (ROH), effective population size (Ne), and linkage disequilibrium (LD) patterns. Thus, the assessment of this information has become essential to the implementation of genomic selection on purebred and crossbred cattle breeding programs. In this way, we assessed the genotype of 19 cattle breeds raised in Brazil belonging to taurine, indicine, synthetic crossbreds, and Iberian-derived locally adapted ancestries to evaluate the overall LD decay patterns, Ne, ROH, and breed composition. We were able to obtain a general overview of the genomic architecture of cattle breeds currently raised in Brazil and other tropical countries. We found that, among the evaluated breeds, different marker densities should be used to improve the genomic prediction accuracy and power of genome-wide association studies. Breeds showing low Ne values indicate a recent inbreeding, also reflected by the occurrence of longer ROH, which demand special attention in the matting schemes to avoid extensive inbreeding. Candidate genes (e.g., ABCA7, PENK, SPP1, IFNAR1, IFNAR2, SPEF2, PRLR, LRRTM1, and LRRTM4) located in the identified ROH islands were evaluated, highlighting biological processes involved with milk production, behavior, rusticity, and fertility. Furthermore, we were successful in obtaining the breed composition regarding the taurine and indicine composition using single-nucleotide polymorphism (SNP) data. Our results were able to observe in detail the genomic backgrounds that are present in each breed and allowed to better understand the various contributions of ancestor breeds to the modern breed composition to the Brazilian cattle.

show abstract

“…Furthermore, we performed the overall survival analysis of 663 immune-related genes and identified that 600 genes (90.5%) were associated with better outcomes in metastatic melanoma patients. PPI network and two significant models were constructed among them and highly connected nodes in the models, including IL7R, CD38 and CXCR4 were closely associated with immune response, especially participating in regulating CD4+ and CD8+ T cells [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Data mining of immune-related prognostic genes in metastatic melanoma microenvironment

et al. 2020

View full text Add to dashboard Cite

Skin cutaneous melanoma (SKCM) is one of the most deadly malignancies. Although immunotherapies showed the potential to improve the prognosis for metastatic melanoma patients, only a small group of patients can benefit from it. Therefore, it is urgent to investigate the tumor microenvironment in melanoma as well as to identify efficient biomarkers in the diagnosis and treatments of SKCM patients. A comprehensive analysis was performed based on metastatic melanoma samples from the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm, including gene expression, immune and stromal scores, prognostic immune-related genes, infiltrating immune cells analysis and immune subtype identification. Then, the differentially expressed genes (DEGs) were obtained based on the immune and stromal scores, and a list of prognostic immune-related genes was identified. Functional analysis and the protein–protein interaction network revealed that these genes enriched in multiple immune-related biological processes. Furthermore, prognostic genes were verified in the Gene Expression Omnibus (GEO) databases and used to predict immune infiltrating cells component. Our study revealed seven immune subtypes with different risk values and identified T cells as the most abundant cells in the immune microenvironment and closely associated with prognostic outcomes. In conclusion, the present study thoroughly analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for metastatic melanoma.

show abstract

Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele

Cited by 42 publications

References 32 publications

Interleukin 7 receptor (IL7R) is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells

Interleukin 7 receptor (IL7R) is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells

Genome-Wide Analyses Reveal the Genetic Architecture and Candidate Genes of Indicine, Taurine, Synthetic Crossbreds, and Locally Adapted Cattle in Brazil

Data mining of immune-related prognostic genes in metastatic melanoma microenvironment

Contact Info

Product

Resources

About