Dataset Information

Regulated expression of nuclear receptor ROR?t confers distinct functional fates to NK cell receptor-expressing ROR?t(+) innate lymphocytes.

ABSTRACT: Whether the recently identified innate lymphocyte population coexpressing natural killer cell receptors (NKRs) and the nuclear receptor ROR?t is part of the NK or lymphoid tissue inducer (LTi) cell lineage remains unclear. By using adoptive transfer of genetically tagged LTi-like cells, we demonstrate that NKR?ROR?t(+) innate lymphocytes but not NK cells were direct progenitors to NKR(+)ROR?t(+) cells in vivo. Genetic lineage tracing revealed that the differentiation of LTi-like cells was characterized by the stable upregulation of NKRs and a progressive loss of ROR?t expression. Whereas interleukin-7 (IL-7) and intestinal microbiota stabilized ROR?t expression within such NKR-LTi cells, IL-12 and IL-15 accelerated ROR?t loss. ROR?t(+) NKR-LTi cells produced IL-22, whereas ROR?t? NKR-LTi cells released IFN-? and were potent inducers of colitis. Thus, the ROR?t gradient in NKR-LTi cells serves as a tunable rheostat for their functional program. Our data also define a previously unappreciated role of ROR?t? NKR-LTi cells for the onset or maintenance of inflammatory bowel diseases.

SUBMITTER: Vonarbourg C

PROVIDER: S-EPMC3042726 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes.

Vonarbourg Cedric C Mortha Arthur A Bui Viet L VL Hernandez Pedro P PP Kiss Elina A EA Hoyler Thomas T Flach Melanie M Bengsch Bertram B Thimme Robert R Hölscher Christoph C Hönig Manfred M Pannicke Ulrich U Schwarz Klaus K Ware Carl F CF Finke Daniela D Diefenbach Andreas A

Immunity 20101101 5

Whether the recently identified innate lymphocyte population coexpressing natural killer cell receptors (NKRs) and the nuclear receptor RORγt is part of the NK or lymphoid tissue inducer (LTi) cell lineage remains unclear. By using adoptive transfer of genetically tagged LTi-like cells, we demonstrate that NKR⁻RORγt(+) innate lymphocytes but not NK cells were direct progenitors to NKR(+)RORγt(+) cells in vivo. Genetic lineage tracing revealed that the differentiation of LTi-like cells was charac ...[more]

PMID: 21093318

Similar Datasets

Project description:A complex network of transcription factors contributes to the establishment and maintenance of the osteoblastic phenotype. Although relatively few transcription factors, such as Runx2 and osterix, are essential to the process of osteoblastic differentiation, others serve the purpose of fine-tuning in response to various environmental and hormonal cues. The nuclear receptor (NR) superfamily of transcription factors are involved in numerous aspects of bone biology. In this study, we characterized the expression pattern of the entire NR superfamily in differentiating primary murine calvarial cells in order to identify novel NR regulatory patterns. Dynamic patterns of NR expression were observed throughout the differentiation process. Interestingly, retinoic acid receptor-related orphan receptor ? (Ror?) expression was markedly suppressed at later stages of differentiation. To gain further insight into the function of NRs in bone biology, the NR superfamily was also profiled in mouse bone marrow precursor cells isolated from either young (6-month) or aging, osteoporotic (18-22-month) mice. Of interest, Ror? was potently overexpressed in the aged cohort. Collectively, these data provided evidence that Ror? expression is inversely correlated with osteogenic potential, suggesting Ror? may be an important and unexplored regulator of osteogenesis. To validate this hypothesis, a cell model stably expressing Ror? in mouse osteoblastic MC3T3-E1 cells was produced (MC3T3-Ror?). These cells displayed markedly suppressed bone nodule formation as well as reduced osteocalcin and osterix gene expression. Because these genes are Runx2 targets, we reasoned that Ror? may interfere with Runx2 activity. Consistent with this, transient transfection analysis demonstrated that Ror? inhibited Runx2-dependent activation of a Runx2-reporter construct. In summary, our data provide a comprehensive profile of NR expression during osteoblast differentiation and identify Ror? as a novel regulator of osteogenesis and potentially of age-related bone loss through antagonism of Runx2 activity.

Dataset Information

Regulated expression of nuclear receptor ROR?t confers distinct functional fates to NK cell receptor-expressing ROR?t(+) innate lymphocytes.

Publications

Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure