Kir3dl2-KO Mouse

Kir3dl2, also known as CD158k, is a member of the killer cell immunoglobulin-like receptor (KIR) family, expressed as a disulfide-linked homodimer on natural killer (NK) cells and rare circulating T lymphocytes, mainly CD8+ [2]. It binds to HLA-A3,-A11, free heavy chain form of HLA-B27 and CpG oligonucleotides (ODN), participating in NK cell development, licensing, and cell activation [2]. KIR3DL2 is a framework gene present in all individuals, suggesting unique functions compared to other KIR family members [2].

KIR3DL2 expression is associated with acute-type adult T-cell leukemia (ATL), different from lymphoma-and chronic/smoldering-type ATL [1]. HTLV-1 infection may trigger KIR3DL2 transcription, which correlates with promoter hypomethylation [1]. In cutaneous T-cell lymphomas such as Sézary syndrome, CD30+ cutaneous lymphoma, and transformed mycosis fungoides, KIR3DL2 is implicated and anti-KIR3DL2 monoclonal antibodies are useful for diagnosis, follow-up, and treatment [2]. In primary cutaneous anaplastic large-cell lymphoma (pcALCL), KIR3DL2 is expressed on tumour cells and the anti-KIR3DL2 antibody IPH4102 can mediate antibody-derived cytotoxicity [3]. In hepatocellular carcinoma (HCC), a reduction in infiltrating NK cells expressing KIR3DL2 in recurrent cases is observed, with these KIR3DL2high NK cells in a quiescent state, suggesting NK cell exhaustion and poor prognosis [4].

In summary, Kir3dl2 is crucial in NK cell-related functions and development. Its abnormal expression is associated with multiple diseases including ATL, cutaneous T-cell lymphomas, and HCC. Research on Kir3dl2 using genetic models could potentially further clarify its role in these disease conditions, providing new insights for diagnosis and treatment strategies.

References:

1. Cheminant, Morgane, Lhermitte, Ludovic, Bruneau, Julie, Marçais, Ambroise, Hermine, Olivier. . KIR3DL2 contributes to the typing of acute adult T-cell leukemia and is a potential therapeutic target. In Blood, 140, 1522-1532. doi:10.1182/blood.2022016765. https://pubmed.ncbi.nlm.nih.gov/35687761/

2. Schmitt, Christian, Marie-Cardine, Anne, Bensussan, Armand. 2017. Therapeutic Antibodies to KIR3DL2 and Other Target Antigens on Cutaneous T-Cell Lymphomas. In Frontiers in immunology, 8, 1010. doi:10.3389/fimmu.2017.01010. https://pubmed.ncbi.nlm.nih.gov/28912774/

3. Battistella, M, Janin, A, Jean-Louis, F, Bagot, M, Michel, L. 2016. KIR3DL2 (CD158k) is a potential therapeutic target in primary cutaneous anaplastic large-cell lymphoma. In The British journal of dermatology, 175, 325-33. doi:10.1111/bjd.14626. https://pubmed.ncbi.nlm.nih.gov/27037558/

4. Zhu, Jie, Jin, Anli, Pan, Baishen, Yang, Wenjing, Wang, Beili. 2024. Exploring the role of KIR3DL2 on NK cells in hepatocellular carcinoma and its potential prognostic implications. In iScience, 27, 110637. doi:10.1016/j.isci.2024.110637. https://pubmed.ncbi.nlm.nih.gov/39262781/