Characterization of the IL-15 niche in primary and secondary lymphoid organs in vivo.
IL-15 is a cytokine critical for development, maintenance, and response of T cells, natural killer (NK) cells, NK T cells, and dendritic cells. However, the identity and distribution of IL-15-expressing cells in lymphoid organs are not well understood. To address these questions, we established and analyzed IL-15-CFP knock-in mice. We found that IL-15 was highly expressed in thymic medulla, and medullary thymic epithelial cells with high MHC class II expression were the major source of IL-15. In bone marrow, IL-15 was detected primarily in VCAM-1(+)PDGFRβ(+)CD31(-)Sca-1(-) stromal cells, which corresponded to previously described CXCL12-abundant reticular cells. In lymph nodes, IL-15-expressing cells were mainly distributed in the T-cell zone and medulla. IL-15 was expressed in some fibroblastic reticular cells and gp38(-)CD31(-) double-negative stromal cells in the T-cell zone. Blood endothelial cells, including all high endothelial venules, also expressed high IL-15 levels in lymph nodes, whereas lymphatic endothelial cells (LECs) lacked IL-15 expression. In spleen, IL-15 was expressed in VCAM-1(+) stromal cells, where its expression increased as mice aged. Finally, IL-15 expression in blood and LECs of peripheral lymphoid organs significantly increased in LPS-induced inflammation. Overall, we have identified and characterized several IL-15-expressing cells in primary and secondary lymphoid organs, providing a unique perspective of IL-15 niche in immune microenvironment. This study also suggests that some stromal cells express IL-7 and IL-15 differentially and suggests a way to functionally classify different stromal cell subsets.
Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Guangwei
G
Cui
Takahiro
T
Hara
Szandor
S
Simmons
Keisuke
K
Wagatsuma
Akifumi
A
Abe
Hitoshi
H
Miyachi
Satsuki
S
Kitano
Masaru
M
Ishii
Shizue
S
Tani-ichi
Koichi
K
Ikuta
D000375:Aging / Q000276:immunology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055879:Gene Knock-In Techniques; D007249:Inflammation / Q000473:pathology; D019409:Interleukin-15 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D019409:Interleukin-15; D008070:Lipopolysaccharides
aging; differentiation; homeostasis; thymus