1dec4737592748534cd092b4e205c90b FroImm_a2026v17n1845279.pdf a7144ff92159502fa8e47ebc5046d896b4837868 FroImm_a2026v17n1845279.pdf bbc9c20e3a92d9a864306fbb8169e52619f19434c0fd8bb2a751bad6d7e7199a FroImm_a2026v17n1845279.pdf Title: Rethinking TYK2 P1104A: a flawed evolutionary trade-off in tuberculosis? Subject: Cardona P-J (2026) Rethinking TYK2 P1104A: a flawed evolutionary trade-off in tuberculosis?. Front. Immunol. 17:1845279. doi: 10.3389/fimmu.2026.1845279 Keywords: evolutionary genetics; host–pathogen interactions; IL-12/IFN-γ axis; IL-23/IL-17 pathway; immune modulation; plague; tuberculosis; TYK2 P1104A Author: Pere-Joan Cardona CreationDate: Fri Jun 12 03:49:42 2026 CEST ModDate: Fri Jun 12 03:49:42 2026 CEST Custom Metadata: no Metadata Stream: yes Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 7 Encrypted: no Page size: 595.389 x 841.663 pts (A4) Page rot: 0 File size: 1589135 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CHCPOD+AdvTTd3a5f740 Type 1C WinAnsi yes yes no 72 0 CHCPPM+AdvTT2c8ce45a+20 Type 1C WinAnsi yes yes no 305 0 CHCPPN+AdvOT94be8fa4.B Type 1C WinAnsi yes yes no 306 0 CHCPPO+AdvOT1ef757c0 Type 1C WinAnsi yes yes no 71 0 CHCPOE+AdvTTd3a5f740+fb Type 1C Custom yes yes yes 307 0 CHCPOF+AdvTT9b12cd41 Type 1C WinAnsi yes yes no 76 0 CHCPOG+AdvTT9b12cd41+01 Type 1C MacRoman yes yes no 308 0 CHCPOH+AdvPSA323 Type 1C WinAnsi yes yes no 309 0 CHCPOI+AdvOT3f84ef53 Type 1C WinAnsi yes yes no 74 0 CHCPOJ+AdvTT9b12cd41+fb Type 1C Custom yes yes yes 77 0 CHCPPK+AdvTTd168d80a.I Type 1C WinAnsi yes yes no 310 0 CHCPPL+AdvTT2c8ce45a Type 1C WinAnsi yes yes no 75 0 CHDBBI+AdvOT1ef757c0+fb Type 1C Custom yes yes yes 73 0 CHDDEL+AdvTT749c1f5a.I Type 1C WinAnsi yes yes no 328 0 CHDDEM+AdvOT1ef757c0+22 Type 1C Custom yes yes yes 151 0 CHDDEN+AdvOT1ef757c0+20 Type 1C WinAnsi yes yes no 150 0 CHDDFO+AdvOT7d6df7ab.I Type 1C WinAnsi yes yes no 329 0 CHDENG+AdvTT9b12cd41+20 Type 1C WinAnsi yes yes no 152 0 CHDEPG+AdvTTd3a5f740+20 Type 1C WinAnsi yes yes no 335 0 CHDFAH+AdvTT58d178b9+03 Type 1C Custom yes yes yes 336 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-07-21 04:16:01 CEST RepresentationInformation: FroImm_a2026v17n1845279.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-07-20 16:32:34 CEST Size: 1589135 Format: PDF Version: 1.4 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 395 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: true NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseOutlines Language: en-US Outlines: Item: Title: Rethinking TYK2 P1104A: a flawed evolutionary trade-off in tuberculosis? Destination: bmark_-2062941931 Children: Item: Title: Introduction Destination: s1 Item: Title: From increased to reduced risk of multiple sclerosis Destination: s2 Item: Title: From non-hierarchical activation to gene dosage Destination: s3 Item: Title: Confirming a low-autoimmunity genotype Destination: s4 Item: Title: Relating TYK2 P1104A to Mycobacterium tuberculosis infection Destination: s5 Item: Title: Bronze Age selection and the tuberculosis hypothesis Destination: s6 Item: Title: IL-12 impairment appears dosage-dependent rather than absolute Destination: s7 Item: Title: Rise and fall of P1104A in West Eurasia: an ecological interpretation Destination: s8 Item: Title: Anti-IL-23 and anti-IL-17 therapies do not support a strong tuberculosis-risk model Destination: s9 Item: Title: Reduced type I IFN signalling via P1104A could represent an additional protective mechanism against TB Destination: s10 Item: Title: A more plausible interpretation Destination: s11 Item: Title: Conclusion Destination: s12 Item: Title: Data availability statement Destination: bmark_-1258588262 Item: Title: Author contributions Destination: bmark_-1208584890 Item: Title: Funding Destination: bmark_1865464027 Item: Title: Conflict of interest Destination: bmark_1089982005 Item: Title: Generative AI statement Destination: bmark_-1453097031 Item: Title: Publisher’s note Destination: bmark_-1256977648 Item: Title: Supplementary material Destination: bmark_632582120 Item: Title: References Destination: bmark_2090415954 Info: Title: Rethinking TYK2 P1104A: a flawed evolutionary trade-off in tuberculosis? Author: Pere-Joan Cardona Subject: Cardona P-J (2026) Rethinking TYK2 P1104A: a flawed evolutionary trade-off in tuberculosis?. Front. 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Front. Immunol. 17:1845279. doi: 10.3389/fimmu.2026.1845279 Copyright © 2026 Cardona. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. evolutionary genetics host–pathogen interactions IL-12/IFN-γ axis IL-23/IL-17 pathway immune modulation plague tuberculosis TYK2 P1104A Rethinking TYK2 P1104A: a flawed evolutionary trade-off in tuberculosis? evolutionary genetics; host–pathogen interactions; IL-12/IFN-γ axis; IL-23/IL-17 pathway; immune modulation; plague; tuberculosis; TYK2 P1104A 2026-06-12T09:49:42+08:00 2026-06-12T09:49:42+08:00 2026-06-12T09:49:42+08:00 True https://www.frontiersin.org/legal/copyright-statement uuid:a7220289-53d6-49ae-8b19-1ded9f8f9c2d uuid:8c0c0a52-d73e-4383-8aac-a7b037d10d83 Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 219, 683, 479, 704 Annotation: Subtype: Link Rect: 219, 658, 508, 679 Annotation: Subtype: Link Rect: 219, 633, 371, 654 Annotation: Subtype: Link Rect: 320, 105, 324, 114 Destination: 19 Annotation: Subtype: Link Rect: 49, 33, 128, 40 Annotation: Subtype: Link Rect: 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