Signalling mechanisms driving homeostatic and inflammatory effects of interleukin-15 on tissue lymphocytes

• Published in: Discovery immunology Vol. 3; no. 1; p. kyae002
• Main Authors: Skariah, Neema, James, Olivia J, Swamy, Mahima
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 2024
• Subjects: T Cells at Barrier Sites; interleukin-15; innate-like T cells; natural killer cells; autoimmunity; signalling
• ISSN: 2754-2483; 2754-2483
• DOI: 10.1093/discim/kyae002

There is an intriguing dichotomy in the function of cytokine interleukin-15-at low levels, it is required for the homeostasis of the immune system, yet when it is upregulated in response to pathogenic infections or in autoimmunity, IL-15 drives inflammation. IL-15 associates with the IL-15Rα within both myeloid and non-haematopoietic cells, where IL-15Rα trans-presents IL-15 in a membrane-bound form to neighboring cells. Alongside homeostatic maintenance of select lymphocyte populations such as NK cells and tissue-resident T cells, when upregulated, IL-15 also promotes inflammatory outcomes by driving effector function and cytotoxicity in NK cells and T cells. As chronic over-expression of IL-15 can lead to autoimmunity, IL-15 expression is tightly regulated. Thus, blocking dysregulated IL-15 and its downstream signalling pathways are avenues for immunotherapy. In this review we discuss the molecular pathways involved in IL-15 signalling and how these pathways contribute to both homeostatic and inflammatory functions in IL-15-dependent mature lymphoid populations, focusing on innate, and innate-like lymphocytes in tissues.