ライフサイエンスコーパス: RORgamma

1 inity synthetic ligand for both RORalpha and RORgamma.

2 requires two nuclear receptors, RORalpha and RORgamma.

3 receptor and the orphan receptors Nur77 and RORgamma.

4 ponse elements (ROREs) that were occupied by RORgamma.

5 )) cells expressing the transcription factor RORgamma.

6 y in Jurkat cells overexpressing RORalpha or RORgamma.

7 )2D3 function as antagonists of RORalpha and RORgamma.

8 ates with the rhythmic expression pattern of RORgamma.

9 acid-related orphan receptors, RORalpha and RORgamma.

10 ation of the rhythmic expression of Prox1 by RORgamma.

11 greatly suppressed in adipose cells lacking RORgamma.

12 incidence of lymphomas was also observed in RORgamma-/- 129/SvEv mice.

13 the retinoid-related orphan receptor gamma (RORgamma), a member of the nuclear receptor superfamily,

14 acid receptor-related orphan receptor gamma (RORgamma), a T-cell-associated transcription factor, in

15 RORgamma-activated Npas2 transcription directly by bindi

16 tively reveal the structural determinants of RORgamma activation, which is critical for designing ROR

17 Pharmacological inhibition of RORgamma activity reduced plasma IL-1beta as well as IL-

18 activation, which is critical for designing RORgamma agonists for cancer immunotherapy.

19 Other orphan receptors including RORalpha2, RORgamma and COUP-TFI are also potentiated by CaMKIV.

20 by TGF-beta and IL-6, which requires STAT3, RORgamma and IL-21.

21 ibiting RORgamma with SR2211, targeting both RORgamma and its isoform RORgammat, increases Tregs and

22 RORgamma and its thymus-specific isoform RORgammat are e

23 ntagonists stabilize the interaction between RORgamma and Prox1.

24 Our results indicate that RORgamma and Rev-Erbalpha are part of a feed-back loop t

25 Prox1 interacts directly with RORgamma and RORalpha and negatively regulates their tra

26 ckout mice indicated that in certain tissues RORgamma and RORalpha exhibited a certain degree of redu

27 The lack of functional RORgamma and RORgammaT isoforms resulted in the absence

28 toma Huh-7 cells increased the expression of RORgamma and several ROR-target genes, along with increa

29 of CD3-CD4+CD45+ cells that normally express RORgamma and that are likely early progenitors of lympho

30 mice deficient for the transcription factor RORgamma and the germline promoters T early-alpha and Ja

31 constituents from E. japonica that modulate RORgamma and/or TGR5 using this newly developed biochemo

32 the retinoid-related orphan receptor gamma (RORgamma) and its possible role in disease.

33 acid receptor-related orphan receptor gamma (RORgamma) and the G protein-coupled bile acid receptor (

34 CD4+ Tconv cells can differentiate into both RORgamma+ and Helios+ pTreg cells, providing a physiolog

35 RORgamma+ and Helios+ Treg cells in the colon are phenot

36 Asthma-associated markers (Gata3, RORgamma, and HLA-DR) were reduced in T- and innate- cel

37 gulated Foxp3 downregulation, whereas STAT3, RORgamma, and ROR* were required for IL-17 expression in

38 Rorgamma, and the T(regs) that express it, contribute su

39 Unexpectedly, leukocytes from RORgamma- and RORgammaT-deficient individuals also displ

40 Conversely, RORgamma antagonist and the reduction of hepatic RORgamm

41 RORgamma antagonists cause tumor regression in patient-d

42 RORgamma antagonists stabilize the interaction between R

43 ceptor-related orphan receptors RORalpha and RORgamma are critical for the functions of specific subs

44 RORalpha and RORgamma are expressed in human skin cells that produce

45 Thus, RORalpha and RORgamma are ligand-regulated members of the NR superfam

46 molecular modeling, identified RORalpha and RORgamma as excellent receptor candidates for the hydrox

47 nic glucocorticoid exposure induces an S1PR2-RORgamma axis to cooperate with GR to enhance hepatic gl

48 The presence of RORgamma binding sites and its down-regulation in RORgam

49 ted transactivation activity of RORalpha and RORgamma but not RORbeta.

50 high affinity ligands for both RORalpha and RORgamma by directly binding to their ligand-binding dom

51 e that ligand-dependent action of the orphan RORgamma can be defined by selectively disrupting putati

52 that is strongly linked to nuclear receptor RORgamma, compared to estrogen receptor-positive breast

53 the rhythmic expression of Avpr1a depends on RORgamma consistent with the concept that RORgamma1 prov

54 sponse was observed in sensitized/challenged RORgamma-deficient animals in vivo.

55 ion was markedly greater in splenocytes from RORgamma-deficient mice following in vitro restimulation

56 In this report, we examine the capacity of RORgamma-deficient mice to develop an adaptive immune re

57 pha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is sho

58 gh primary CD4 T cell expansion is normal in RORgamma-deficient mice, the persistence of memory CD4 T

59 oter in the liver of wild-type mice, but not RORgamma-deficient mice.

60 lar observations were made in liver-specific RORgamma-deficient mice.

61 udies of mice deficient in the expression of RORgamma demonstrated that this receptor plays a crucial

62 ce, the persistence of memory CD4 T cells is RORgamma-dependent.

63 In this study, we demonstrate that RORgamma directly regulates Npas2 expression in vivo.

64 Our studies indicate that loss of RORgamma disturbs homeostasis in the thymus by enhancing

65 ce we demonstrate that LTi cells are the key RORgamma-expressing cell type sufficient for memory CD4

66 Presentation of peptide:MHCII by RORgamma-expressing group 3 innate lymphoid cells (ILC3s

67 A microbe-induced population of RORgamma-expressing regulatory T cells (Tregs) is essent

68 amma antagonist and the reduction of hepatic RORgamma expression attenuated such glucocorticoid effec

69 h nodes and Peyer's patches, indicating that RORgamma expression is indispensable for lymph node orga

70 ospective analysis in patients revealed that RORgamma expression may predict pancreatic cancer aggres

71 cells stably expressing a Tet-on RORalpha or RORgamma expression vector and a ROR-responsive element

72 ct Rorg promoters that control RORgammaT and RORgamma expression, respectively.

73 ession of RAR-related orphan receptor gamma (RORgamma) expression.

74 lear receptor superfamily, mice deficient in RORgamma function were generated by targeted disruption.

75 We demonstrate that RORgamma functions as an essential activator of the enti

76 Altogether, our study indicates that RORgamma functions as an important link between the circ

77 radiation bone marrow chimeras revealed that RORgamma functions in an iNKT cell lineage-specific mann

78 ed IMQ-induced changes, with an imbalance of Rorgamma+ gammadeltaT cells.

79 ough key transcription factors (TFs; Helios, Rorgamma, Gata3, and cMaf), but their interrelationships

80 tion seemed to be RORalpha-specific, because RORgamma had little effect.

81 Hence, RORgamma has critical functions in T cell repertoire sel

82 The key TFs (Rorgamma, Helios, Gata3, and cMaf) play different roles,

83 LC2 (IL-5 and IL-13-expressing nuocytes) and RORgamma ILC (IL-17 and IL-22-expressing 'ILC3') are imp

84 uding RORgamma(+) ILC3s into wounded dermis; RORgamma(+) ILC3s are potent sources of IL17F in wounds

85 Mice deficient for RORgamma(+) ILC3s heal wounds poorly resulting from dela

86 recruitment of immune cell subsets including RORgamma(+) ILC3s into wounded dermis; RORgamma(+) ILC3s

87 Inversely, overexpression of RORgamma in hepatoma Hepa1-6 cells greatly induced the e

88 These results illustrate a major role for RORgamma in regulation of innate immunity via modulation

89 ylases CYP27B1 and CYP24A1, and RORalpha and RORgamma in the human uveal tract and uveal melanomas.

90 These data reveal a critical role for RORgamma in the regulation of Ig production and Th1/Th2

91 ecific orphan nuclear receptors RORalpha and RORgamma in vivo.

92 receptors (ROR) alpha (RORalpha) and gamma (RORgamma) in these tissues.

93 were predominantly immature, insensitive to RORgamma-inducing bacterial cues and to IL6, and showed

94 RORgamma inhibition disrupts its association with SREBP2

95 Upon RORgamma inhibition, RNA sequencing showed strongly incr

96 natorial treatment of t(4;11) cells with the RORgamma inhibitor showed additive effects with cytarabi

97 "drug-likeness" indices, an orally available RORgamma inhibitor, JTE-151, was finally generated and w

98 A number of RORgamma inhibitors have been reported over the past dec

99 that inhibiting the NLRP3 inflammasome with RORgamma inverse agonists may be an effective method to

100 Additionally, RORgamma inverse agonists reduced mortality in an LPS/d-

101 RORgamma inverse agonists suppressed lipopolysaccharide

102 Additionally, the ability of the RORgamma inverse agonists to suppress IL-1beta secretion

103 rgeting the NLRP3 inflammasome in vivo using RORgamma inverse agonists was examined in two models: LP

104 RORgamma inverse agonists were effective inhibitors of t

105 The orphan nuclear receptor RORgamma is a key regulator for T helper 17 (TH17) cell

106 Our observations indicate that RORgamma is essential for lymphoid organogenesis and pla

107 Similar to RORgammaT, RORgamma is selectively expressed in Th17 cells and is e

108 tion factor Rorgamma, paradoxically, in that Rorgamma is thought to antagonize FoxP3 and to promote T

109 RAR-related orphan receptor gamma (RORgamma) is a nuclear receptor that plays an essential

110 Overexpression of one or more Rorgamma isoforms in >77% of the tumors tested may compl

111 depletion of nuclear receptors RORalpha and RORgamma, key components of the molecular circadian cloc

112 acid-receptor-related orphan receptor gamma (RORgamma), known to drive inflammation and T cell differ

113 d reduce binding of a corepressor peptide to RORgamma LBD.

114 These ligands bind directly to recombinant RORgamma ligand binding domain (LBD), promote recruitmen

115 To date, no endogenous RORgamma ligands have been described.

116 mma binding sites and its down-regulation in RORgamma-/- liver suggest that the rhythmic expression o

117 We have identified the Rorgamma locus as an integration site in 19% of TBLV-ind

118 lacking the orphan nuclear hormone receptor RORgamma lose thymic expression of the anti-apoptotic fa

119 In sham-treated mice lacking RORgamma, low-grade pulmonary inflammation was observed

120 When placed in culture, the RORgamma-/- lymphoblastic cells underwent accelerated "s

121 s suggest that pharmacological repression of RORgamma may represent a strategy for treatment of obesi

122 e-2(-/-) mice as recipients and wild-type or RORgamma(-/-) mice as donors, respectively, demonstrate

123 The thymus of RORgamma(-/-) mice contains 74.4% +/- 8.9% fewer thymocy

124 However, RORgamma(-/-) mice have 2- to 3-fold more splenocytes th

125 e acid pool size was considerably reduced in RORgamma(-/-) mice in part through its regulation of sev

126 The increase in B lymphocytes in RORgamma(-/-) mice is caused neither by abnormal B cell

127 nstrate that the splenic microenvironment of RORgamma(-/-) mice is defective, since wild-type T and B

128 RORgamma(-/-) mice lack peripheral and mesenteric lymph

129 y of Npas2 mRNA expression was maintained in RORgamma(-/-) mice, the peak level of expression was sig

130 as altered due to a lowered thymic output in RORgamma(-/-) mice.

131 hase of the cell cycle among thymocytes from RORgamma(-/-) mice.

132 optotic cells in the cortex of the thymus of RORgamma(-/-) mice.

133 that changes in homeostasis in the thymus of RORgamma-/- mice are associated with a high incidence of

134 No other tumor types were detected in any of RORgamma-/- mice that died during the course of the expe

135 ermore, the characterization of a library of RORgamma modulators reveals that structural dynamics of

136 Our findings support a model in which RORgamma negatively controls apoptosis in thymocytes.

137 eptors alpha and gamma (RORalpha (NR1F1) and RORgamma (NR1F3)) are orphan nuclear receptors and perfo

138 t the mutant, restored thymocyte survival in RORgamma null mice.

139 ow-derived macrophages (BMDMs) isolated from RORgamma-null mice displayed reduced capacity to secrete

140 acid receptor-related orphan receptor-gamma (RORgamma or RORc) continues to evolve, significant effor

141 ermore, analyses of BM chimeras using either RORgamma(-/-) or recombinase-activating gene-2(-/-) mice

142 id receptor-related orphan receptor C (RORc, RORgamma, or NR1F3) is a nuclear receptor that plays a m

143 of an RORgammat antagonist, ursolic acid, in RORgamma- or RORgammat-dependent cell-based reporter ass

144 Hepatic RORgamma overexpression in hepatic S1PR2 knockdown mice

145 al species-requires the transcription factor Rorgamma, paradoxically, in that Rorgamma is thought to

146 acid receptor-related orphan receptor gamma (RORgamma) plays a key role in regulating the balance bet

147 acid receptor-related orphan receptor gamma (RORgamma) plays important roles in thymocyte development

148 ectrum of phenotypes between the Helios+ and Rorgamma+ poles, different Treg-inducing bacteria induci

149 ies were identified as potential risks for a RORgamma program.

150 re-existing tTregs, could differentiate into RORgamma+ pTregs upon interaction with gut microbiota.

151 f a number of lipid metabolic genes, loss of RORgamma reduced the level of several lipids in liver an

152 Genetic and pharmacological inhibition of RORgamma reduces tumor cholesterol content and synthesis

153 on (QPCR) analysis demonstrated that in vivo RORgamma regulate these genes directly and in a Zeitgebe

154 Collectively, these results suggest that RORgamma regulates lymphocyte homeostasis at multiple le

155 d mutation analysis support the concept that RORgamma regulates the transcription of several lipid me

156 nges in innate lymphocytes, macrophages, and RORgamma(+) regulatory T (T(reg)) cells.

157 ce the differentiation of a distinct pool of RORgamma(+) regulatory T (Treg) cells crucial for intest

158 cells that express the transcription factor RORgamma, regulatory (Treg), or conventional (Th17) are

159 Thus, the marked context-specificity of Rorgamma results in very different outcomes even in clos

160 ystal structures of the LBDs of RORalpha and RORgamma revealed docking scores for 20(OH)D3, 20,23(OH)

161 In this study, we show that RORgamma robustly regulates the rhythmic expression of s

162 Analysis of RORgamma/RORalpha double knockout mice indicated that in

163 d systemic immunity to Mycobacterium require RORgamma, RORgammaT, or both.

164 Thus, Th17 immunity is controlled by a Rel-RORgamma-RORgammaT axis, and strategies targeting Rel/NF

165 These findings indicate the ability of RORgamma/RORgammat inhibition to modulate specific T-cel

166 Rorgamma's transcriptional footprint differs in colonic

167 n that the small molecule inverse agonist of RORgamma SR1555 [1-(4-((4'-(1,1,1,3,3,3-hexafluoro-2-hyd

168 required for T(H)17 differentiation, such as RORgamma t (encoded by Rorc) and the cytokine IL21.

169 Following hybridoma stimulation, RORgamma t also inhibits IL-2 production but does not af

170 he thymus expressed the transcription factor RORgamma t and the IL-23 receptor.

171 cytokine production, as well as induction of RORgamma t and the IL-23R.

172 he ligand-binding and DNA-binding domains of RORgamma t are required for this effect.

173 rylation and reduced expression of IL-17 and RORgamma t compared with wild-type cells.

174 ptional regulator; STAT3 deficiency impaired RORgamma t expression and led to elevated expression of

175 We propose that the role of RORgamma t expression in immature thymocytes is to inhib

176 e addition of IL21 nor the overexpression of RORgamma t fully restores IL17 production in Batf(-/-) T

177 Ectopic expression of RORgamma t protects T cell hybridomas from activation-in

178 id receptor-related orphan receptor gamma-T (RORgamma t), a THi-specific transcriptional regulator; S

179 We have identified RORgamma t, a novel, thymus-specific isoform of the orph

180 on of the Th17-specific transcription factor RORgamma t.

181 s not caused by a difference in the level of RORgamma t.

182 ring fetal life the nuclear hormone receptor RORgamma(t) is expressed exclusively in and is required

183 urvival, was up-regulated by radio-resistant RORgamma(t)(+)CCR6(+)NKp46(-) lymphoid tissue inducer ce

184 RORgamma(t+) LTi cells provide essential factors, among

185 of the intestinal BA pool increases colonic RORgamma(+ )T(reg) cell counts and ameliorates host susc

186 expansion and differentiation of intestinal RORgamma(+) T cells.

187 retinoic acid-related orphan receptor gamma (RORgamma)t-regulated thymocyte survival in vivo.

188 mus of germ-free RORgammat-gfp and IL-6(-/-) RORGamma: t-gfp mice, indicating that these cells do not

189 cific isoform of the orphan nuclear receptor RORgamma that is expressed predominantly in CD4+ CD8+ do

190 agonists or inverse agonists of RORalpha and RORgamma, that opens new possibilities for local (skin)

191 RORgamma, the most recently identified member of the ROR

192 enous and synthetic ligands for RORalpha and RORgamma, thereby solidifying their function as ligand-d

193 RORgamma thus regulates the survival of CD4+8+ thymocyte

194 RORgamma(-/-) thymocytes placed in culture exhibit a dra

195 eous" apoptosis at a rate similar to that of RORgamma-/- thymocytes.

196 d promoter activity through interaction with Rorgamma to repress Rorgamma transactivation and by inte

197 The enhanced recruitment of RORgamma to ROREs in their promoter region, increased hi

198 Inhibition of RORalpha and RORgamma transactivation activities in a Tet-on CHO cell

199 through interaction with Rorgamma to repress Rorgamma transactivation and by interacting with Rev-erb

200 anism underlying the rheostatic functions of RORgamma(+) Treg cells in compromised tissues.

201 ion to drive the accumulation of gut-derived RORgamma(+) Treg cells in injured muscle, wherein they r

202 RORgamma(+) Treg proportions negatively correlated with

203 RORgamma(+) Treg proportions varied between inbred mouse

204 rnal transmission, in an immunoglobulin- and RORgamma(+) Treg-dependent manner.

205 monocolonized mice revealed that Helios+ and Rorgamma+ Tregs are related and cannot be uniquely equat

206 elios+ Tregs being completely dependent, but RORgamma+ Tregs largely independent.

207 Reporter gene analysis showed that RORgamma was able to induce reporter gene activity throu

208 RORgamma was also required for development of lymph node

209 ChIP analysis demonstrated that RORgamma was recruited to this promoter in the liver of

210 The activation of Npas2 by RORgamma was repressed by co-expression with Rev-Erbalph

211 eceptor (RAR)-related orphan receptor gamma (RORgamma), which acts upstream of SREBP2 and serves as m

212 ctes with SR1555 represses the expression of RORgamma while leading to increased expression of FGF21

213 e ligand binding domain (LBD) of RORalpha or RORgamma with an LBD-interacting LXXLL-peptide, were use

214 7 was found to directly bind to RORalpha and RORgamma with high affinity (K(i) = 132 and 51 nM, respe

215 It was hypothesized that inhibiting RORgamma with SR2211, targeting both RORgamma and its is