Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire

Guerder, Sylvie; Hassel, Chervin; Carrier, Alice

doi:10.1007/s00251-018-1078-y

Cited by 8 publications

(6 citation statements)

References 57 publications

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“…The region on SSC7 harbors the highest significantly associated SNP obtained from single-locus analyses. ALGA0039405 is located in PRSS16 , which acts in T-cell development and antigen-presenting pathways and is associated with human diabetes susceptibility (Guerder et al, 2018). Taking into account genes containing at least suggestive significant markers, the list of positional candidates in this QTL region further comprises phosphate transporters ( SLC17A1 and SLC17A4 ) and nucleosome-related genes ( HIST1H3E , HIST1H1D , and HMGN4 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic Contribution to Variation in Blood Calcium, Phosphorus, and Alkaline Phosphatase Activity in Pigs

et al. 2019

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Blood values of calcium (Ca), inorganic phosphorus (IP), and alkaline phosphatase activity (ALP) are valuable indicators for mineral status and bone mineralization. The mineral homeostasis is maintained by absorption, retention, and excretion processes employing a number of known and unknown sensing and regulating factors with implications on immunity. Due to the high inter-individual variation of Ca and P levels in the blood of pigs and to clarify molecular contributions to this variation, the genetics of hematological traits related to the Ca and P balance were investigated in a German Landrace population, integrating both single-locus and multi-locus genome-wide association study (GWAS) approaches. Genomic heritability estimates suggest a moderate genetic contribution to the variation of hematological Ca ( N = 456), IP ( N = 1049), ALP ( N = 439), and the Ca/P ratio ( N = 455), with values ranging from 0.27 to 0.54. The genome-wide analysis of markers adds a number of genomic regions to the list of quantitative trait loci, some of which overlap with previous results. Despite the gaps in knowledge of genes involved in Ca and P metabolism, genes like THBS2 , SHH , PTPRT , PTGS1 , and FRAS1 with reported connections to bone metabolism were derived from the significantly associated genomic regions. Additionally, genomic regions included TRAFD1 and genes coding for phosphate transporters ( SLC17A1 – SLC17A4 ), which are linked to Ca and P homeostasis. The study calls for improved functional annotation of the proposed candidate genes to derive features involved in maintaining Ca and P balance. This gene information can be exploited to diagnose and predict characteristics of micronutrient utilization, bone development, and a well-functioning musculoskeletal system in pig husbandry and breeding.

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Section: Discussionmentioning

confidence: 99%

Genetic Contribution to Variation in Blood Calcium, Phosphorus, and Alkaline Phosphatase Activity in Pigs

et al. 2019

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“…The thymic cortex provides the microenvironment for positive selection of conventional T-cells and early Tregs. Thus, its cTECs generate distinctive self-peptides via a unique set of proteases: (a) to select CD8 + thymocytes, cytosolic peptides are generated for presentation on MHCI molecules by the cortex-restricted ‘thymoproteasome’, with its unique Beta5t subunit (encoded by PSMB11 ) [ 28 ]; (b) to select CD4 + thymocytes, MHCII molecules in cTECs are loaded inside LAMP2 + endosomes with various endogenous self-peptides generated using cathepsin L and the thymus-specific serine protease, TSSP (encoded by CTSL and PRSS16 , respectively) [ 139 ]. Autophagy in cTECs is one source of such MHCII:peptide complexes [ 30 ]; they also owe their persistence on the cTEC surface to CD83-dependent blockade of MACH-8-mediated trafficking there [ 140 , 141 ].…”

Section: The Thymic Cortex and Autoimmunitymentioning

confidence: 99%

Thymus and autoimmunity

et al. 2021

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The thymus prevents autoimmune diseases through mechanisms that operate in the cortex and medulla, comprising positive and negative selection and the generation of regulatory T-cells (Tregs). Egress from the thymus through the perivascular space (PVS) to the blood is another possible checkpoint, as shown by some autoimmune/immunodeficiency syndromes. In polygenic autoimmune diseases, subtle thymic dysfunctions may compound genetic, hormonal and environmental cues. Here, we cover (a) tolerance-inducing cell types, whether thymic epithelial or tuft cells, or dendritic, B- or thymic myoid cells; (b) tolerance-inducing mechanisms and their failure in relation to thymic anatomic compartments, and with special emphasis on human monogenic and polygenic autoimmune diseases and the related thymic pathologies, if known; (c) polymorphisms and mutations of tolerance-related genes with an impact on positive selection (e.g. the gene encoding the thymoproteasome-specific subunit, PSMB11), promiscuous gene expression (e.g. AIRE, PRKDC, FEZF2, CHD4), Treg development (e.g. SATB1, FOXP3), T-cell migration (e.g. TAGAP) and egress from the thymus (e.g. MTS1, CORO1A); (d) myasthenia gravis as the prototypic outcome of an inflamed or disordered neoplastic ‘sick thymus’.

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“…Another endosomal peptidase, thymus-specific serine protease (TSSP, also known as Prss16), is also abundant in cTECs. Studies using MHC-II-restricted TCR transgenic mice showed that TSSP contributes to the production of positively selecting MHC-II-associated self-peptides (40)(41)(42). TSSP is also reported to play a role in the production of negatively selecting MHC-II-associated self-peptides, influencing the severity of autoimmune inflammation in type 1 diabetes in the NOD mouse strain (43)(44)(45).…”

Section: Mhc-ii-associated Self-peptide Production In Ctecsmentioning

confidence: 99%

Thymus machinery for T-cell selection

Kondo

Ohigashi

Takahama

2018

International Immunology

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An immunocompetent and self-tolerant pool of naive T cells is formed in the thymus through the process of repertoire selection. T cells that are potentially capable of responding to foreign antigens are positively selected in the thymic cortex and are further selected in the thymic medulla to help prevent self-reactivity. The affinity between T-cell antigen receptors expressed by newly generated T cells and self-peptide-major histocompatibility complexes displayed in the thymic microenvironments plays a key role in determining the fate of developing T cells during thymic selection. Recent advances in our knowledge of the biology of thymic epithelial cells have revealed unique machinery that contributes to positive and negative selection in the thymus. In this article, we summarize recent findings on thymic T-cell selection, focusing on the machinery unique to thymic epithelial cells.

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Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire

Cited by 8 publications

References 57 publications

Genetic Contribution to Variation in Blood Calcium, Phosphorus, and Alkaline Phosphatase Activity in Pigs

Genetic Contribution to Variation in Blood Calcium, Phosphorus, and Alkaline Phosphatase Activity in Pigs

Thymus and autoimmunity

Thymus machinery for T-cell selection

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