Cytotoxic lymphocytes, such as natural killer (NK) cells, protect our body from pathogens and cancer. However, when their functions are deregulated, these cells can promote uncontrolled inflammation. In addition to NK cells, innate lymphoid cells (ILCs) also have been identified as a type of killer cell type. The functions of NK cells and ILCs are regulated by specific networks of transcription factors. In this publication, the researchers found that the transcription factor known as STAT4 is a main regulator of inflammatory and cytotoxic activity among ILCs during intestinal inflammation.

What is exciting about this article?

Understanding the mechanisms that regulate the functions of cytotoxic innate lymphocytes is particularly relevant in the context of human inflammatory bowel disease. It may also have implications for the design of cancer and antiviral therapeutics.

Grant support


Research Areas:

Cell Biology Immunology Molecular Biology and Biochemistry


Divergent roles for STAT4 in shaping differentiation of cytotoxic ILC1 and NK cells during gut inflammation.

Scarno G, Mazej J, Laffranchi M, Di Censo C, Mattiola I, Candelotti AM, Pietropaolo G, Stabile H, Fionda C, Peruzzi G, Brooks SR, Tsai WL, Mikami Y, Bernardini G, Gismondi A, Sozzani S, Di Santo JP, Vosshenrich CAJ, Diefenbach A, Gadina M, Santoni A, Sciumè G
Proc Natl Acad Sci U S A.
2023 Oct 3;
doi: 10.1073/pnas.2306761120
PMID: 37756335

Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.