In vivo availability of the cytokine IL-7 constrains the survival and homeostasis of peripheral iNKT cells.

Joo-Young Park, Hee Yeun Won, Devon T DiPalma, Hye Kyung Kim, Tae-Hyoun Kim, Can Li, Noriko Sato, Changwan Hong, Ninan Abraham, Ronald E Gress, Jung-Hyun Park

Cell reports 2022 Jan 11

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Understanding the homeostatic mechanism of invariant natural killer T (iNKT) cells is a critical issue in iNKT cell biology. Because interleukin (IL)-15 is required for the thymic generation of iNKT cells, IL-15 has also been considered necessary for the homeostasis of peripheral iNKT cells. Here, we delineated the in vivo cytokine requirement for iNKT cells, and we came to the surprising conclusion that IL-7, not IL-15, is the homeostatic cytokine for iNKT cells. Employing a series of experimental mouse models where the availability of IL-7 or IL-15 was manipulated in peripheral tissues, either by genetic tools or by adult thymectomy and cytokine pump installation, we demonstrate that the abundance of IL-7, and not IL-15, limits the size of the peripheral iNKT cell pool. These results redefine the cytokine requirement for iNKT cells and indicate competition for IL-7 between iNKT and conventional αβ T cells. Copyright © 2021. Published by Elsevier Inc.

Citation

Joo-Young Park, Hee Yeun Won, Devon T DiPalma, Hye Kyung Kim, Tae-Hyoun Kim, Can Li, Noriko Sato, Changwan Hong, Ninan Abraham, Ronald E Gress, Jung-Hyun Park. In vivo availability of the cytokine IL-7 constrains the survival and homeostasis of peripheral iNKT cells. Cell reports. 2022 Jan 11;38(2):110219