In a recent article, Sen Santara et al. demonstrated that the activating natural killer (NK) cell receptor NKp46 binds to externalized calreticulin (ecto-CRT), leading to NK cell degranulation and target cell killing. They show that endoplasmic reticulum stress-induced ecto-CRT serves as a danger-associated molecular pattern, helping NK cells identify and eliminate infected, malignant, stressed or senescent cells.
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http://dx.doi.org/10.1111/imcb.12659 | DOI Listing |
Immunol Rev
January 2025
W. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, Maryland, USA.
Natural killer (NK) cells are essential elements of the innate immune response against tumors and viral infections. NK cell activation is governed by NK cell receptors that recognize both cellular (self) and viral (non-self) ligands, including MHC, MHC-related, and non-MHC molecules. These diverse receptors belong to two distinct structural families, the C-type lectin superfamily and the immunoglobulin superfamily.
View Article and Find Full Text PDFClin Rev Allergy Immunol
December 2024
The 2nd Department of Gynecology Oncology of Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People's Republic of China.
NKp46 is a natural killer cell activating receptor primarily expressed on NK cells and non-NK innate lymphoid cells. In the context of anti-infection, NKp46 activates NK cells by binding to ligands on pathogens or infected cells, enabling NK cells to kill the infected cells. In antitumor activities, NKp46 plays a pivotal role in combating tumor growth through mechanisms such as directly killing tumor cells, inhibiting tumor immune escape, and reducing tumor growth rate through immune editing.
View Article and Find Full Text PDFImmune Netw
October 2024
Immune Research Institute, Seegene Medical Foundation, Seoul 04805, Korea.
NK cells are specialized immune effector cells crucial for triggering immune responses against aberrant cells. Although recent advancements have concentrated on creating or releasing T-cell responses specific to tumor Ags, the clinical advantages of this approach have been limited to certain groups of patients and tumor types. This emphasizes the need for alternative strategies.
View Article and Find Full Text PDFProtein Eng Des Sel
January 2024
Department of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA, 94305, United States.
Recent developments in cancer immunotherapy have highlighted the potential of harnessing natural killer (NK) cells in the treatment of neoplastic malignancies. Of these, bispecific antibodies, and NK cell engager (NKCE) protein therapeutics in particular, have been of interest. Here, we used phage display and yeast surface display to engineer RLN131, a unique cross-reactive antibody that binds to human, mouse, and cynomolgus NKp46, an activating receptor found on NK cells.
View Article and Find Full Text PDFNat Commun
July 2024
Laboratory of Systems Immunology, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
Group 3 innate lymphoid cells (ILC3) are crucial for maintaining mucosal homeostasis and regulating inflammatory diseases, but the molecular mechanisms governing their phenotype and function are not fully understood. Here, we show that ILC3s highly express Fcer1g gene, which encodes the antibody Fc-receptor common gamma chain, FcεR1γ. Genetic perturbation of FcεR1γ leads to the absence of critical cell membrane receptors NKp46 and CD16 in ILC3s.
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