Maristella Steri, Valeria Orrù, Carlo Sidore, Antonella Mulas, Maristella Pitzalis, Fabio Busonero, Andrea Maschio, Valentina Serra, Mariano Dei, Sandra Lai, Francesca Virdis, Monia Lobina, Annalisa Loizedda, Michele Marongiu, Marco Masala, Matteo Floris, Nicolò Curreli, Lenuta Balaci, Francesco Loi, Maria Grazia Pilia, Alessandro Delitala, Edoardo Fiorillo, David Schlessinger, Magdalena Zoledziewska
{"title":"TYK2: p。Pro1104Ala变异通过调节免疫细胞水平预防自身免疫","authors":"Maristella Steri, Valeria Orrù, Carlo Sidore, Antonella Mulas, Maristella Pitzalis, Fabio Busonero, Andrea Maschio, Valentina Serra, Mariano Dei, Sandra Lai, Francesca Virdis, Monia Lobina, Annalisa Loizedda, Michele Marongiu, Marco Masala, Matteo Floris, Nicolò Curreli, Lenuta Balaci, Francesco Loi, Maria Grazia Pilia, Alessandro Delitala, Edoardo Fiorillo, David Schlessinger, Magdalena Zoledziewska","doi":"10.1111/imm.13902","DOIUrl":null,"url":null,"abstract":"<p>The <i>TYK2</i>:p.Pro1104Ala (rs34536443) hypomorph variant has been associated with protection against numerous autoimmune disorders. Thus, its mechanism of action becomes of great interest. Here, consistent with the participation of activated immune cells in autoimmunity, we show that the variant regulates the levels of immune cells at a human, general population level and is associated particularly with higher levels of T and B lymphocytes, especially the naïve (non-activated) compartment. Also, consistent with a protective function in autoimmunity, the level of regulatory CD4+ T cells was increased. Thus, this variant decreases immune activation thereby protecting from autoimmunity. Our work links the cellular mechanism regulated by the <i>TYK2</i>:p.Pro1104Ala variant to autoimmunity protection and supports TYK2 as a therapeutic target in autoimmunity.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 4","pages":"462-469"},"PeriodicalIF":4.9000,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13902","citationCount":"0","resultStr":"{\"title\":\"TYK2:p.Pro1104Ala Variant Protects Against Autoimmunity by Modulating Immune Cell Levels\",\"authors\":\"Maristella Steri, Valeria Orrù, Carlo Sidore, Antonella Mulas, Maristella Pitzalis, Fabio Busonero, Andrea Maschio, Valentina Serra, Mariano Dei, Sandra Lai, Francesca Virdis, Monia Lobina, Annalisa Loizedda, Michele Marongiu, Marco Masala, Matteo Floris, Nicolò Curreli, Lenuta Balaci, Francesco Loi, Maria Grazia Pilia, Alessandro Delitala, Edoardo Fiorillo, David Schlessinger, Magdalena Zoledziewska\",\"doi\":\"10.1111/imm.13902\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The <i>TYK2</i>:p.Pro1104Ala (rs34536443) hypomorph variant has been associated with protection against numerous autoimmune disorders. Thus, its mechanism of action becomes of great interest. Here, consistent with the participation of activated immune cells in autoimmunity, we show that the variant regulates the levels of immune cells at a human, general population level and is associated particularly with higher levels of T and B lymphocytes, especially the naïve (non-activated) compartment. Also, consistent with a protective function in autoimmunity, the level of regulatory CD4+ T cells was increased. Thus, this variant decreases immune activation thereby protecting from autoimmunity. Our work links the cellular mechanism regulated by the <i>TYK2</i>:p.Pro1104Ala variant to autoimmunity protection and supports TYK2 as a therapeutic target in autoimmunity.</p>\",\"PeriodicalId\":13508,\"journal\":{\"name\":\"Immunology\",\"volume\":\"174 4\",\"pages\":\"462-469\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-01-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13902\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/imm.13902\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/imm.13902","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
TYK2:p.Pro1104Ala Variant Protects Against Autoimmunity by Modulating Immune Cell Levels
The TYK2:p.Pro1104Ala (rs34536443) hypomorph variant has been associated with protection against numerous autoimmune disorders. Thus, its mechanism of action becomes of great interest. Here, consistent with the participation of activated immune cells in autoimmunity, we show that the variant regulates the levels of immune cells at a human, general population level and is associated particularly with higher levels of T and B lymphocytes, especially the naïve (non-activated) compartment. Also, consistent with a protective function in autoimmunity, the level of regulatory CD4+ T cells was increased. Thus, this variant decreases immune activation thereby protecting from autoimmunity. Our work links the cellular mechanism regulated by the TYK2:p.Pro1104Ala variant to autoimmunity protection and supports TYK2 as a therapeutic target in autoimmunity.
期刊介绍：
Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers.
Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology.
The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.
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