TYK2:p.Pro1104Ala Variant Protects Against Autoimmunity by Modulating Immune Cell Levels

IF 4.9 3区医学 Q2 IMMUNOLOGY Immunology Pub Date : 2025-01-21 DOI:10.1111/imm.13902

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

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Abstract

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.

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TYK2: p。Pro1104Ala变异通过调节免疫细胞水平预防自身免疫

TYK2: p。Pro1104Ala （rs34536443）低变形变体与许多自身免疫性疾病的保护有关。因此，它的作用机制成为极大的兴趣。在这里，与激活的免疫细胞参与自身免疫一致，我们表明该变体调节人类，一般人群水平的免疫细胞水平，特别是与较高水平的T和B淋巴细胞，特别是naïve（非激活）区相关。此外，与自身免疫的保护功能一致，调节性CD4+ T细胞水平升高。因此，这种变异降低了免疫激活，从而防止自身免疫。我们的工作将TYK2:p调控的细胞机制联系起来。Pro1104Ala变体具有自身免疫保护作用，支持TYK2作为自身免疫的治疗靶点。

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来源期刊

Immunology 医学-免疫学

CiteScore

11.90

自引率

1.60%

发文量

175

审稿时长

4-8 weeks

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.