酪氨酸激酶2（TYK2）：第1104位脯氨酸突变为丙氨酸的变体通过调节免疫细胞水平预防自身免疫。
TYK2 :p.Pro1104Ala Variant Protects Against Autoimmunity by Modulating Immune Cell Levels.
作者信息
Steri Maristella, Orrù Valeria, Sidore Carlo, Mulas Antonella, Pitzalis Maristella, Busonero Fabio, Maschio Andrea, Serra Valentina, Dei Mariano, Lai Sandra, Virdis Francesca, Lobina Monia, Loizedda Annalisa, Marongiu Michele, Masala Marco, Floris Matteo, Curreli Nicolò, Balaci Lenuta, Loi Francesco, Pilia Maria Grazia, Delitala Alessandro, Fiorillo Edoardo, Schlessinger David, Zoledziewska Magdalena
机构信息
Institute of Genetic and Biomedical Research (IRGB), Italian National Research Council (CNR), Monserrato, Sardinia, Italy.
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
出版信息
Immunology. 2025 Apr;174(4):462-469. doi: 10.1111/imm.13902. Epub 2025 Jan 21.
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.
酪氨酸激酶2（TYK2）基因的p.Pro1104Ala（rs34536443）低表达变体与预防多种自身免疫性疾病有关。因此，其作用机制备受关注。在此，与活化免疫细胞参与自身免疫过程一致，我们发现该变体在人类普通人群水平上调节免疫细胞水平，尤其与较高水平的T淋巴细胞和B淋巴细胞相关，特别是初始（未活化）亚群。此外，与在自身免疫中的保护功能一致，调节性CD4 + T细胞水平升高。因此，该变体降低免疫激活，从而预防自身免疫。我们的研究将由TYK2:p.Pro1104Ala变体调节的细胞机制与自身免疫保护联系起来，并支持将TYK2作为自身免疫的治疗靶点。
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