title: Interleukin-22 drives endogenous thymic regeneration in mice.
abstract: Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection, or immunodepletion. However, the mechanisms governing this regeneration remain poorly understood. We detail such a mechanism, centered on interleukin-22 (IL-22) and triggered by the depletion of CD4(+)CD8(+) double-positive thymocytes. Intrathymic levels of IL-22 were increased after thymic insult, and thymic recovery was impaired in IL-22-deficient mice. IL-22, which signaled through thymic epithelial cells and promoted their proliferation and survival, was up-regulated by radio-resistant RORγ(t)(+)CCR6(+)NKp46(-) lymphoid tissue inducer cells after thymic injury in an IL-23-dependent manner. Administration of IL-22 enhanced thymic recovery after total body irradiation. These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence.
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. dudakovj@mskcc.org
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Dudakov
authors.forename: Alan M
authors.initials: AM
authors.lastname: Hanash
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jenq
authors.forename: Lauren F
authors.initials: LF
authors.lastname: Young
authors.forename: Arnab
authors.initials: A
authors.lastname: Ghosh
authors.forename: Natalie V
authors.initials: NV
authors.lastname: Singer
authors.forename: Mallory L
authors.initials: ML
authors.lastname: West
authors.forename: Odette M
authors.initials: OM
authors.lastname: Smith
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Holland
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Tsai
authors.forename: Richard L
authors.initials: RL
authors.lastname: Boyd
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival; D003713:Dendritic Cells / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D053759:Interleukin-23 / Q000378:metabolism; D007378:Interleukins / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D011829:Radiation Dosage; D018123:Receptors, Interleukin / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D012038:Regeneration; D015398:Signal Transduction; D060168:Thymocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000502:physiology* / Q000528:radiation effects; D015854:Up-Regulation; D014916:Whole-Body Irradiation; D000097043:Interleukin-22
chemical_list: D053759:Interleukin-23; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D000097043:Interleukin-22; C539901:Rorc protein, mouse; C415369:interleukin-22 receptor