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Record W1748436622 · doi:10.1126/science.aaa4282

Impairment of immunity to <i>Candida</i> and <i>Mycobacterium</i> in humans with bi-allelic <i>RORC</i> mutations

2015· article· en· W1748436622 on OpenAlexfundno aff
Satoshi Okada, Janet Markle, Elissa K. Deenick, Federico Mele, Diana Averbuch, Macarena Lagos, Mohammed Alzahrani, Saleh Al‐Muhsen, Rabih Halwani, S. Cindy, Natalie Wong, Claire Soudais, Lauren A. Henderson, Hiyam Marzouqa, Jamal Shamma, Marcela González, Rubén Martínez‐Barricarte, Chizuru Okada, Danielle T. Avery, Daniela Latorre, Caroline Deswarte, Fabienne Jabot‐Hanin, Egídio Torrado, Jeffrey J. Fountain, Aziz Belkadi, Yuval Itan, Bertrand Boisson, Mélanie Migaud, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Sylvain Breton, James McCluskey, Jamie Rossjohn, Jean‐Pierre de Villartay, Despina Moshous, Sophie Hambleton, Sylvain Latour, Peter D. Arkwright, Capucine Pïcard, Olivier Lantz, Dan Engelhard, Masao Kobayashi, Laurent Abel, Andrea M. Cooper, Luigi D. Notarangelo, Stéphanie Boisson‐Dupuis, Anne Puel, Federica Sallusto, Jacinta Bustamante, Stuart G. Tangye, Jean‐Laurent Casanova

Bibliographic record

VenueScience · 2015
Typearticle
Languageen
FieldImmunology and Microbiology
TopicNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Canadian institutionsnot available
FundersNational Center for Research ResourcesJapan Society for the Promotion of ScienceNational Health and Medical Research CouncilCanadian Institutes of Health ResearchSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Institutes of HealthHelmut Horten StiftungAXA Research FundInstitut National de la Santé et de la Recherche MédicaleNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Allergy and Infectious DiseasesUniversité Paris DescartesHoward Hughes Medical InstituteNational Center for Advancing Translational SciencesAgence Nationale de la RechercheEuropean Molecular Biology OrganizationSt. Giles FoundationH2020 European Research CouncilRockefeller University
KeywordsRAR-related orphan receptor gammaImmune systemImmunityBiologyImmunologyCytokineGenetics

Abstract

fetched live from OpenAlex

Human inborn errors of immunity mediated by the cytokines interleukin-17A and interleukin-17F (IL-17A/F) underlie mucocutaneous candidiasis, whereas inborn errors of interferon-γ (IFN-γ) immunity underlie mycobacterial disease. We report the discovery of bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional RORγ and RORγT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORγ- and RORγT-deficient individuals also displayed an impaired IFN-γ response to Mycobacterium. This principally reflected profoundly defective IFN-γ production by circulating γδ T cells and CD4(+)CCR6(+)CXCR3(+) αβ T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORγ, RORγT, or both.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.253
Teacher spread0.235 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations415
Published2015
Admission routes1
Has abstractyes

Explore more

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