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

doi:10.1016/j.celrep.2021.110219

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

Cell Rep. 2022 Jan 11;38(2):110219. doi: 10.1016/j.celrep.2021.110219.

Authors

Affiliations

¹ Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 10, Room 5B17, 10 Center Drive, Bethesda, MD 20892, USA; Department of Oral and Maxillofacial Surgery, Seoul National University School of Dentistry, Seoul National University Dental Hospital, 101 Daehakno, Jongno-gu, Seoul 03080, South Korea. Electronic address: bbyoung1@snu.ac.kr.
² Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 10, Room 5B17, 10 Center Drive, Bethesda, MD 20892, USA.
³ Experimental Transplantation Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
⁴ Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
⁵ Department of Anatomy, Pusan National University School of Medicine, Yangsan 626-870, South Korea.
⁶ Department of Microbiology and Immunology, and Department of Zoology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
⁷ Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 10, Room 5B17, 10 Center Drive, Bethesda, MD 20892, USA. Electronic address: Parkhy@mail.nih.gov.

Abstract

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.

Keywords: STAT5; apoptosis; common γ chain; thymectomy; thymus.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Animals
Cell Differentiation / immunology*
Cytokines / metabolism
Female
Homeostasis
Interleukin-7 / immunology
Interleukin-7 / metabolism*
Male
Mice
Mice, Inbred C57BL
Natural Killer T-Cells / immunology
Natural Killer T-Cells / metabolism*

Substances

Cytokines
Interleukin-7

Grants and funding

ZIA BC011214/ImNIH/Intramural NIH HHS/United States