Lcp2-KO Mouse

Lcp2, also known as Lymphocyte cytosolic protein 2 or SLP-76, is a member of the SLP-76 family of adapters. It is essential for the development and activation of T cells, regulating immunoreceptor signaling (such as T-cell receptors) and is required for integrin signaling in neutrophils and platelets. It is involved in multiple immune-related pathways and plays a significant role in the body's immune response [1,2].

In a patient with biallelic Lcp2 variants, there was combined immunodeficiency and impaired PI3K signaling. The patient had decreased neutrophil function, numbers of unswitched and class-switched memory B cells, and serum IgA. Intracellular SLP76 protein levels were reduced in B cells, CD4+ and CD8+ T cells, and natural killer cells. Tonic and ligand-induced levels of phosphorylated ribosomal protein S6 and ligand-induced phosphorylated PLCγ1 were decreased in B cells and CD4+ and CD8+ T cells, indicating that biallelic variants in Lcp2 can cause combined immunodeficiency with early-onset immune dysregulation [3]. In metastatic skin cutaneous melanoma, Lcp2 upregulation was associated with good overall survival, and high Lcp2 expression was positively correlated with more tumor-infiltrating CD8+ T cells. It also served as a prognostic biomarker for progression-free survival of patients receiving anti-PD1 immunotherapy [1].

In conclusion, Lcp2 is crucial for T-cell development and activation, and its dysregulation can lead to immunodeficiency and impact immune-related disease outcomes such as in metastatic melanoma. Studies on Lcp2, including those with loss-of-function variants in patients, help to understand its role in immune-related biological processes and disease conditions, potentially guiding the development of immunotherapies and providing prognostic insights.

References:

1. Wang, Zijun, Peng, Mou. 2021. A novel prognostic biomarker LCP2 correlates with metastatic melanoma-infiltrating CD8+ T cells. In Scientific reports, 11, 9164. doi:10.1038/s41598-021-88676-9. https://pubmed.ncbi.nlm.nih.gov/33911146/

2. Iyer, Vaishnavi Srinivasan, Boddul, Sanjaykumar V, Johnsson, Anna-Karin, Phan, Anh Tuân, Wermeling, Fredrik. 2022. Modulating T-cell activation with antisense oligonucleotides targeting lymphocyte cytosolic protein 2. In Journal of autoimmunity, 131, 102857. doi:10.1016/j.jaut.2022.102857. https://pubmed.ncbi.nlm.nih.gov/35780036/

3. Edwards, Emily S J, Ojaimi, Samar, Ngui, James, O'Hehir, Robyn E, van Zelm, Menno C. 2023. Combined immunodeficiency and impaired PI3K signaling in a patient with biallelic LCP2 variants. In The Journal of allergy and clinical immunology, 152, 807-813.e7. doi:10.1016/j.jaci.2023.04.020. https://pubmed.ncbi.nlm.nih.gov/37211057/