The activation of CD4+ T cells, a type of white blood cell that is responsible for both disease-protective and disease-promoting immune responses, requires metabolic changes to meet the energy demands of their rapid growth and proliferation. This study indicated that interleukin-2 (IL-2), a secretory cytokine protein produced by CD4+ T cells, plays a key role in T cell metabolism by activating another key intracellular signaling protein, STAT5. This study demonstrated for the first time how the IL-2-STAT5 signaling cascade regulates T cell growth and proliferation by cooperating with other nuclear transcription factors that are likely to be relevant in lymphoid malignancies.

What is exciting about this article?

How T cells obtain the energy to sustain a powerful immune response has been a subject of speculation. By using a mouse model, this study established that a previously identified cytokine signaling pathway, known as the IL-2-STAT5 pathway, plays a central role in CD4+ T cell metabolism and growth, and that high STAT5 activity in T cells might be linked to lymphoid malignancies. This study’s findings are likely to help advance immunotherapy of lymphoid cancer.

How does this fit into the larger NIAMS portfolio?

The focus of Dr. O’Shea’s laboratory is to discover the molecular basis of various cytokine signaling pathways that control contrasting immune responses. The lab has decoded how T cells gain strength to grow and proliferate during disease, when they are needed most. Specifically, the findings allow us to better understand how cytokine signaling pathways promote CD4+ T cells metabolism to sustain an effective T cell response.

Grant support


Research Areas:

Cell Biology Clinical Research Computational Biology Genetics and Genomics Immunology


A central role for STAT5 in the transcriptional programing of T helper cell metabolism.

Villarino AV, Laurence AD, Davis FP, Nivelo L, Brooks SR, Sun HW, Jiang K, Afzali B, Frasca D, Hennighausen L, Kanno Y, O'Shea JJ
Sci Immunol.
2022 Nov 25;
doi: 10.1126/sciimmunol.abl9467
PMID: 36427325

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