title: NIK-dependent RelB activation defines a unique signaling pathway for the development of V alpha 14i NKT cells.
abstract: A defect in RelB, a member of the Rel/nuclear factor (NF)-kappa B family of transcription factors, affects antigen presenting cells and the formation of lymphoid organs, but its role in T lymphocyte differentiation is not well characterized. Here, we show that RelB deficiency in mice leads to a selective decrease of NKT cells. RelB must be expressed in an irradiation-resistant host cell that can be CD1d negative, indicating that the RelB expressing cell does not contribute directly to the positive selection of CD1d-dependent NKT cells. Like RelB-deficient mice, aly/aly mice with a mutation for the NF-kappa B-inducing kinase (NIK), have reduced NKT cell numbers. An analysis of NK1.1 and CD44 expression on NKT cells in the thymus of aly/aly mice reveals a late block in development. In vitro, we show that NIK is necessary for RelB activation upon triggering of surface receptors. This link between NIK and RelB was further demonstrated in vivo by analyzing RelB+/- x aly/+ compound heterozygous mice. After stimulation with alpha-GalCer, an antigen recognized by NKT cells, these compound heterozygotes had reduced responses compared with either RelB+/- or aly/+ mice. These data illustrate the complex interplay between hemopoietic and nonhemopoietic cell types for the development of NKT cells, and they demonstrate the unique requirement of NKT cells for a signaling pathway mediated by NIK activation of RelB in a thymic stromal cell.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Elewaut
authors.forename: Raziya B
authors.initials: RB
authors.lastname: Shaikh
authors.forename: Kirsten J L
authors.initials: KJ
authors.lastname: Hammond
authors.forename: Hilde
authors.initials: H
authors.lastname: De Winter
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Leishman
authors.forename: Stephane
authors.initials: S
authors.lastname: Sidobre
authors.forename: Olga
authors.initials: O
authors.lastname: Turovskaya
authors.forename: Theodore I
authors.initials: TI
authors.lastname: Prigozy
authors.forename: Lisa
authors.initials: L
authors.lastname: Ma
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Banks
authors.forename: David
authors.initials: D
authors.lastname: Lo
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.forename: Hilde
authors.initials: H
authors.lastname: Cheroutre
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002678:Chimera; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D053259:Lymphotoxin beta Receptor; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010581:Peyer's Patches / Q000033:anatomy & histology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D018960:Hyaluronan Receptors; D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018124:Receptors, Tumor Necrosis Factor; D051841:Transcription Factor RelB; D014157:Transcription Factors; D001613:beta 2-Microglobulin; D000097782:NF-kappaB-Inducing Kinase; C505699:Ltbr protein, mouse; C497594:Relb protein, mouse