Research Project:
CD56+Cd20+ Doğal Öldürücü Hücre Attipinin Özellikleri ve Multiple Skleroz Hastalığının Prognozuyla İlişkisinin İncelenmesi

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TB.00552

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Albayrak, Özgür
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CD20+ natural killer cells are polyfunctional, memory-like cells that are enriched in inflammatory disorders
(Oxford Univ Press, 2025) Albayrak, Özgür; Tiryaki, Ergün; Kızılırmak, Ali Burak; Doran, Tansu; Gökmenoğlu, Gökçe; Yüksel, Muhammed; Ulukan, Bürge; Arıkan, Çiğdem; Vural, Seçil; Zeybel, Müjdat; Vural, Atay; Akkaya, Nazan; Ulukan, Bürge; Tiryaki, Ergün; Akkaya, Nazan; Doran, Tansu; Kızılırmak, Ali Burak; Uzulmez, Mina; Baytekin, Isil; Soylu, Onder Kemal; Esendagli, Gunes; Meinl, Ingrid; Koseoglu, Mesrure; Yuksel, Burcu; Erus, Suat; Soysal, Aysun; Meinl, Edgar; KUTTAM (Koç University Research Center for Translational Medicine); Graduate School of Health Sciences; School of Medicine; Yes; Gökmenoğlu, Gökçe; SCHOOL OF MEDICINE; GRADUATE SCHOOL OF HEALTH SCIENCES; Research Center
While CD20 was initially characterized as a B cell-specific marker, its expression on memory T cells has expanded our understanding of this molecule's distribution and function. Here, we identify a previously unrecognized CD20-expressing NK cell population and demonstrate its functional significance. CD56(+)CD20(+) NK cells exhibit hallmarks of cellular activation, including elevated NKp46, CD69, and CD137 expression, enhanced proliferative capacity, and increased production of inflammatory cytokines (IFN-gamma, GM-CSF, TNF-alpha, IL-10). Functional analyses revealed enhanced cytotoxicity against K562 targets, correlating with increased expression of cytolytic mediators including granzymes A, B, and K, perforin, FASL, and TRAIL. Single-cell transcriptional profiling demonstrated that MS4A1-expressing NK cells possess a distinct molecular signature characterized by elevated granzyme K expression and memory-like features. These cells preferentially localize to secondary lymphoid organs and accumulate in inflammatory tissues. Notably, CD56(+)CD20(+) NK cells are enriched in multiple inflammatory conditions, including multiple sclerosis, autoimmune hepatitis, hepatitis B infection, hepatocellular carcinoma, and lung cancer. Treatment with rituximab depletes this population, suggesting potential therapeutic implications. Our findings establish CD20(+) NK cells as a functionally distinct lymphocyte subset with enhanced effector capabilities and tissue-homing properties, providing new insights into immune regulation in inflammatory diseases.

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