ライフサイエンスコーパス: insulitis

1 ans, depleting insulin-secreting beta-cells (insulitis).

2 +) cells) into and around pancreatic islets (insulitis).

3 HOT-100% (P < 0.005) and paralleled by lower insulitis.

4 s of their antigen specificity and to induce insulitis.

5 with older female counterparts with advanced insulitis.

6 revent diabetes and block the progression of insulitis.

7 ability of immunomodulatory agents to clear insulitis.

8 es development even at a time of significant insulitis.

9 a recurrence and revealed beta-cell loss and insulitis.

10 ype 1 diabetes (T1D) is preceded by invasive insulitis.

11 e target organ level in patients with active insulitis.

12 1D when administered late after the onset of insulitis.

13 of nondiabetic animals exhibited pancreatic insulitis.

14 ibited diabetes in NOD mice with established insulitis.

15 phase, the ablation of DC led to accelerated insulitis.

16 ocalized loss of IDO and the acceleration of insulitis.

17 nts from the latter to the former suppressed insulitis.

18 circulation and lead to development of peri-insulitis.

19 y within pancreatic islets, correlating with insulitis.

20 x15(null) mice, preceding the development of insulitis.

21 notably inflammatory bowel disease (IBD) and insulitis.

22 Rag-1-/-pfn-/- mice also resulted in IBD and insulitis.

23 e LTbetaR-Ig-treated mice were devoid of any insulitis.

24 wed donor-specific tolerance and reversal of insulitis.

25 ontaneous T1D and a significant reduction in insulitis.

26 d65 DRlyp/lyp animals possessed eosinophilic insulitis.

27 4- plus pIL10-treated recipients was free of insulitis.

28 infiltration into the pancreatic islets, or insulitis.

29 oportion of anti-inflammatory macrophages in insulitis.

30 onset, increased its incidence, and worsened insulitis.

31 BALB/c mice (but with neither alone) induced insulitis.

32 tochemical evidence of increased destructive insulitis.

33 s with insulitis compared with those without insulitis.

34 rexpressed in human T1D islets affected with insulitis.

35 tomically associated with the development of insulitis.

36 gression to diabetes even after the onset of insulitis.

37 ession of inflammatory genes and exacerbated insulitis.

38 ling compared with NOD mice that do not have insulitis.

39 ions yielded significantly greater levels of insulitis.

40 ally decreased the incidence of diabetes and insulitis.

41 ominent surrounding immune cells in areas of insulitis.

42 ine tissue without the presence of prominent insulitis.

43 ed in diabetic islets and regions exhibiting insulitis.

44 onversion from peri-insulitis to destructive insulitis.

45 Insulitis affected 33% of insulin(+) islets compared wit

46 iabetes and greatly reduced the intensity of insulitis after poly I:C treatment.

47 Here we report that islets exhibiting insulitis also manifested proliferation of beta-cells th

48 Insulitis also occurs in the BDC2.5 TCR transgenic line

49 tected their NOD offspring from diabetes and insulitis, an effect that was dependent on the intestina

50 und that DORmO.RAG2(-/-) mice do not develop insulitis and are completely protected from diabetes, de

51 utoimmune diabetes in NOD mice by inhibiting insulitis and augmenting regulatory T cells (Tregs) with

52 and lower affinity TCRs could mediate potent insulitis and autoimmune diabetes, suggesting that TCR a

53 major role in pathogenesis characterized by insulitis and beta cell destruction leading to clinical

54 esult in a deregulation of cells involved in insulitis and beta cell destruction.

55 Methods to diagnose insulitis and beta-cell mass changes during this asympto

56 D-B7-1B-transgenic mice) resulted in reduced insulitis and completely protected NOD mice from develop

57 ssion is a phenotype that is associated with insulitis and correlates with overall disease progressio

58 nduction the mice display similar degrees of insulitis and decrements in the beta cell mass, only tra

59 IL-4 exhibited an accelerated progression of insulitis and developed early diabetes.

60 ith genes that contribute to protection from insulitis and diabetes (Idd3, Idd5, Idd10, and Idd18), t

61 n the nonobese diabetic (NOD) model of TIDM, insulitis and diabetes are dependent on the presence of

62 NOD.IFNAR1(-/-) mice developed insulitis and diabetes at a similar rate to NOD controls

63 Experiments were performed to measure insulitis and diabetes development.

64 eficiency in the NOD mouse completely blocks insulitis and diabetes due to defects both in the initia

65 ayed diabetes in heterozygous females and no insulitis and diabetes in most homozygous female mice.

66 transfer, BDC T cells rapidly induced severe insulitis and diabetes in NOD.scid mice, whereas those f

67 ose streptozotocin (MLDS) induce lymphocytic insulitis and diabetes in rodents.

68 In spite of specific tolerance insulitis and diabetes occurred with normal kinetics ind

69 OVA in pancreatic islet cells induces acute insulitis and diabetes only if endogenous lymphocytes, i

70 autoantibody-mediated K/BxN model, organized insulitis and diabetes onset were unabated, despite a bl

71 t was "added-back" to mice lacking total DC, insulitis and diabetes were restored.

72 ed diabetes is lacking, we sought to produce insulitis and diabetes with either PolyIC and/or B:9-23

73 to partially protect congenic NOD mice from insulitis and diabetes, and to partially tolerize islet-

74 nction would alter the onset or magnitude of insulitis and diabetes, we used transgenic mice expressi

75 ghly susceptible or resistant to AI4-induced insulitis and diabetes.

76 d the mice were monitored for development of insulitis and diabetes.

77 d protected the mice from the development of insulitis and diabetes.

78 , peptide 286-300 (G286), are protected from insulitis and diabetes.

79 Sn-H2(b)), which have near zero incidence of insulitis and diabetes.

80 association of autoantibody expression with insulitis and diabetes.

81 ucial for the spontaneous development of NOD insulitis and diabetes.

82 infiltrates and inhibited the development of insulitis and diabetes.

83 f conversion from peri-insulitis to invasive insulitis and diabetes.

84 abetes (Idd) loci control the development of insulitis and diabetes.

85 ckcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis.

86 a(2)(Itgb2) and alphaL (ItgaL) in developing insulitis and frank diabetes.

87 dd5 subregions were required to protect from insulitis and fully restore self-tolerance.

88 gnificantly delayed, and mice developed less insulitis and had reduced frequencies of beta-cell-autor

89 n, c-Rel deficiency dramatically accelerated insulitis and hyperglycemia in NOD mice along with a sub

90 COS was indispensable for the development of insulitis and hyperglycemia in NOD mice.

91 maintained on acidic pH water (AW) developed insulitis and hyperglycemia rapidly compared with those

92 young mutant mice precipitates the onset of insulitis and hyperglycemia.

93 Early treatment with LTbetaR-Ig prevented insulitis and IDDM, suggesting that LT plays a critical

94 as well as significantly reduced severity of insulitis and improved beta-cell mass, when compared wit

95 d in islets from nonobese diabetic mice with insulitis and in rodent or human beta cells exposed in v

96 s those from BDC-Idd9 mice mediated a milder insulitis and induced diabetes with a significantly dela

97 CCL2 by insulin-producing cells can lead to insulitis and islet destruction.

98 e may represent a viable strategy to prevent insulitis and islet destruction.

99 de may represent a novel strategy to prevent insulitis and islet destruction.

100 at donor islets contained beta cells without insulitis and lacked glucose-stimulated insulin secretio

101 of CXCR1/2 was associated with inhibition of insulitis and modification of leukocytes distribution in

102 T cells into the pancreatic islets, reduced insulitis and mononuclear cell infiltration, and promote

103 the transition from peri-insulitis to intra-insulitis and occurred in obese A(vy)/MIP-TF mice but no

104 ibody production and prevents development of insulitis and overt diabetes.

105 g term protection against the development of insulitis and overt diabetes.

106 stration of AAV vIL-10 significantly reduced insulitis and prevented diabetes development in NOD mice

107 ice with Flt3-ligand significantly decreased insulitis and progression to diabetes and was associated

108 e JNK2 protein kinase) decreased destructive insulitis and reduced disease progression to diabetes.

109 ti-CD137-treated mice are not protected from insulitis and still harbor pathogenic T-cells, as demons

110 male recipients prevented the progression of insulitis and subsequent development of overt IDDM.

111 lts implicate chemokines as key mediators of insulitis and suggest that their blockade may represent

112 fecal transfer significantly suppressed the insulitis and T1D incidence in mice that were on AW but

113 nto 10-wk-old NOD mice prevented spontaneous insulitis and T1D, and the inhibitory effect was further

114 ells (nTregs) induce tolerance that inhibits insulitis and T1D, the in vivo cellular mechanisms under

115 the day of infection protected the rats from insulitis and T1D.

116 se, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet

117 ptide effectively blocked the progression of insulitis and the development of diabetes.

118 he expression of the mIg transgene increased insulitis and the incidence of diabetes compared with tr

119 Additionally, the degree of insulitis and the infiltration of CD8(+) T-cells in the

120 es reveal a correlation between incidence of insulitis and the number of islets showing loss of peri-

121 ckdown of tsg-6 were ineffective at delaying insulitis and the onset of diabetes in mice.

122 nic (Tg) littermates, SOCS-1-Tg mice develop insulitis and their splenocytes transfer disease to NODs

123 d A(vy)/MIP-TF mice developed moderate intra-insulitis and transient hyperglycemia.

124 lls accompanied by a significant decrease in insulitis and type 1 diabetes frequency.

125 d in the BBDR rat, which develops pancreatic insulitis and type 1A-like diabetes after infection with

126 -wk-old NOD mice before the typical onset of insulitis and was detected in B10 mice congenic for the

127 icient NOD (NODBim(-/-)) mice developed less insulitis and were protected from diabetes.

128 e expression profiling at day (d) 40 (before insulitis) and d65 (before disease onset) was conducted

129 function and mass, islet inflammation (i.e., insulitis), and autoantibodies specific for beta-cell an

130 cy of Foxp3+ and IL-10+ T cells, less severe insulitis, and a significant delay in the onset of hyper

131 rk activated in pancreatic beta cells during insulitis, and Arl6ip5, Tnfrsf10b, Traf2, and Ubc are ke

132 -producing cells, significant suppression of insulitis, and delay of the onset of hyperglycemia.

133 (+) DC led to the loss of T cell activation, insulitis, and diabetes mediated by CD4(+) T cells.

134 d the onset of T1D, attenuated the degree of insulitis, and improved pancreatic beta cell mass in a d

135 nstrained effector T cells to nondestructive insulitis, and increased numbers of intraislet FOXP3+ Tr

136 s by approximately 95%, decreased subsequent insulitis, and prevented diabetes in >60% of littermates

137 inhibit T cell activation, ablates invasive insulitis, and restores euglycemia, immune tolerance to

138 sient elevation in their blood glucose, peri-insulitis, and Th1 responses to EGFP which did not sprea

139 Autoimmune diabetes, insulitis, and the infiltrating cellular populations wer

140 gulating autoimmunity in the early stages of insulitis, and the loss of IL-13Ralpha1 on islet-reactiv

141 gulatory T-cell (CD4+CD25+Foxp3+) frequency, insulitis, and/or beta-cell area.

142 stages of type 1 diabetes phenotype, before insulitis appears, we measured insulin autoantibodies (I

143 This implies that the two forms of insulitis are differentially aggressive and that patient

144 Insulitis arises during an asymptomatic phase, prior to

145 These results portray insulitis as a dynamic lesion at all stages of disease,

146 VH281, with limited insulin binding develop insulitis but are protected from TIDM.

147 In vivo, the TCR transgenic mice developed insulitis but not spontaneous diabetes.

148 CD137 was dispensable for the development of insulitis but played a role to promote progression to ov

149 process was remarkable for not only showing insulitis, but also inflammatory destruction of the exoc

150 ABT-induced IL-4 and humoral responses, and insulitis, but enhanced IL-10 and Treg responses and pro

151 mory-phenotype lymphocytes trafficked to the insulitis, but Foxp3(+) regulatory T cells circulated le

152 The inhibitor could prevent or clear insulitis, but had minimal influence on the transcriptom

153 oislet transplantation and displayed reduced insulitis, but independently from the graft.

154 f the nonobese diabetic (NOD) strain develop insulitis, but there is considerable variation in their

155 c animals into DORmO.RAG2(-/-) mice promoted insulitis by OVA-specific CD4(+) T cells.

156 Pervasive insulitis can be reduced by expression of the Idd3 and I

157 he pancreatic islets by autoimmune cells, or insulitis, can persist for long periods of time before t

158 AhR activation prevented the development of insulitis caused by the depletion of Foxp3(+) cells, dem

159 , more robust insulin secretion, and reduced insulitis compared with control animals.

160 in young BBdp rat islets before the onset of insulitis compared with control BBc rats.

161 of lymphocyte infiltration in islet and less insulitis compared with that of the control groups.

162 cantly higher in type 1 diabetes donors with insulitis compared with those without insulitis.

163 )(/)(-) mice exhibited accelerated, invasive insulitis, corresponding to increased CD4(+) and CD8(+)

164 The rAAV-IL-10 therapy attenuated pancreatic insulitis, decreased MHC II expression on CD11b+ cells,

165 high prevalence of IAAs and a high degree of insulitis, despite a nearly complete resistance to diabe

166 lopment of insulin autoantibodies (IAAs) and insulitis, despite the recipients' pancreatic islets lac

167 r (GM-CSF) and interleukin-3 (IL-3) manifest insulitis, destruction of insulin-producing beta cells,

168 s of a small number of genes before onset of insulitis determine the disease progression.

169 vivo, immunization with the EXO accelerates insulitis development in nonobese diabetes-resistant mic

170 When islets were examined in treated mice, insulitis development was blocked at early (3 wk) but no

171 on of CD4 T cells in the pancreas and led to insulitis development.

172 ate BDC cells did not change during invasive insulitis development.

173 gesting that LT plays a critical role in the insulitis development.

174 ivery mode was seen on diabetes incidence or insulitis development.

175 O in NOD mice peaks at a crucial time during insulitis development.

176 oceeds to diabetes or whether a steady state insulitis develops that can be maintained.

177 In contrast, insulitis did not depend on SFB colonization.

178 nTreg depletion led to accelerated invasive insulitis dominated by CD11c(+) dendritic cells (ISL-DCs

179 These results demonstrated invasive insulitis dominated by DCs, not CD4(+) T cells, preceded

180 The quantitative traits of insulitis either alone or combined with age at type 1 di

181 e involved in the series of events provoking insulitis; for example, it may play a role in the physio

182 We determined insulitis frequency (the percent of islets displaying in

183 significant correlation was observed between insulitis frequency and CD45(+), CD3(+), CD4(+), CD8(+),

184 Insulitis frequency showed a significant but limited inv

185 inst diabetes, whereas Tregs expanded during insulitis had minimal mTGF-beta and could not protect ag

186 ops full-blown immune-mediated diabetes with insulitis, hyperglycemia, and hypoinsulinemia.

187 at 12 weeks of age, mATG reversed pancreatic insulitis, improved metabolic responses to glucose chall

188 eptor (TCR) transgenic mice with spontaneous insulitis in F1 mice (FVB x NOD) and spontaneous diabete

189 Descriptions of insulitis in human islets throughout the natural history

190 Reduced insulitis in L-AGE versus H-AGE mice (P < 0.01) was mark

191 detect vascular leakage in association with insulitis in murine models of type 1 diabetes, permittin

192 e in preventing diabetes, but none prevented insulitis in nondiabetic recipients.

193 FP infection induced a more pronounced intra-insulitis in older, more obese, A(vy)/MIP-TF mice.

194 es, RAE1 expression was sufficient to induce insulitis in older, unmanipulated transgenic mice that w

195 uronan (HA) are characteristic of autoimmune insulitis in patients with type 1 diabetes (T1D), but th

196 and spleen and delayed onset of diabetes and insulitis in the NODrag1(-/-) lymphocyte adoptive transf

197 was higher, during the onset of destructive insulitis in the PLNs of nonobese diabetic (NOD) mice.

198 ialitis did not correlate with the degree of insulitis in the same animal and was less sensitive to a

199 We recently reported that insulitis in type 1 diabetes of mice and humans is prece

200 We could detect the onset and evolution of insulitis in vivo and in real time, permitting us to stu

201 e BBDR strain, we observed a time-dependent, insulitis-independent pancreatic upregulation of Ccl11 i

202 olute and were monitored for diabetes onset, insulitis, infiltrating cells, immune cell function, and

203 Despite a lack of insulitis, insulin 1 homozygous knockout mice spontaneou

204 othesis that inflammatory mechanisms trigger insulitis, insulin resistance, faulty insulin signaling,

205 gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the isl

206 Invasive insulitis is a destructive T cell-dependent autoimmune p

207 estruction of beta-cells, but rather because insulitis is abrogated.

208 Insulitis is an important pathological feature of autoim

209 ntervention at early pathogenic stages, when insulitis is first developing.

210 We show that insulitis is transferred to NOD-scid/gammac(null)/A2 mic

211 s do not spontaneously develop diabetes, and insulitis is virtually undetectable.

212 mice with zymosan resulted in suppression of insulitis, leading to a significant delay in hyperglycem

213 eta-cells, where chronic local inflammation (insulitis) leads to beta-cell destruction.

214 amined T cells in pancreas, the diabetogenic insulitis lesion, and lymphoid tissues have revealed a b

215 ions, was not impaired in these disorganized insulitis lesions.

216 Furthermore, pancreatic insulitis levels were not diminished in 9-wk-old NOD.IFN

217 ion with a spherical indenter and found that insulitis made islets mechanically soft compared with co

218 y, we reported that two distinct patterns of insulitis occur in patients with recent-onset T1D from t

219 cohorts and confirm that the two profiles of insulitis occur more widely.

220 rat insulin promoter induces nondestructive insulitis on a nonautoimmune background.

221 No signs of insulitis or autoimmune (type 1) diabetes were observed

222 ulin did not develop insulin autoantibodies, insulitis or autoimmune diabetes, in contrast with mice

223 limination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the

224 islet Ag presentation or on the induction of insulitis or diabetes in either transfer or spontaneous

225 f nonobese diabetic mice that have developed insulitis or diabetes.

226 HLA-DQ nor HLA-DR transgenic mice developed insulitis or spontaneous diabetes.

227 hen NOD mice were allowed to progress to the insulitis phase, the ablation of DC led to accelerated i

228 unable to suppress the disease in 10-wk-old insulitis-positive animals whose diabetogenic T cells ha

229 functions against diabetes in young vs older insulitis-positive mice.

230 g-GAD expanded Tregs in both young and older insulitis-positive, nonobese diabetic (NOD) mice, but de

231 low-dose anti-CD3, this treatment stabilized insulitis, preserved functional beta-cell mass, and rest

232 TY720 treatment of NOD mice with established insulitis prevents the development of diabetes.

233 ) mice with FTY720 before the development of insulitis prevents the onset of diabetes.

234 21R expression renders NOD mice resistant to insulitis, production of insulin autoantibodies, and ons

235 n decreases on islet-resident macrophages as insulitis progresses in the NOD mouse.

236 Blockade of HMGB1 significantly inhibited insulitis progression and diabetes development in both 8

237 otent innate immune mediator contributing to insulitis progression and diabetes onset.

238 week until 25 weeks of age and monitored for insulitis progression and diabetes onset.

239 with age, and their numbers correlated with insulitis progression.

240 nteraction with the Idd5 locus to potentiate insulitis progression.

241 CD8(+), and CD20(+) cell numbers within the insulitis (r = 0.53-0.73, P = 0.004-0.04), but not CD68(

242 icant suppression of the late progression of insulitis, reduced infiltration of islets by autoreactiv

243 tes incidence in association with 1) reduced insulitis, reflected by reductions in CD4(+) T cells and

244 nset diabetic NOD mice led to elimination of insulitis, regeneration of host beta cells, and reversal

245 development of a critical threshold level of insulitis requires neither IL-4 nor IFN-gamma.

246 The insulitis score in aPC-treated mice was 50% less than th

247 Insulitis scores were significantly higher and frequency

248 iabetic mice receiving HOT-100% showed lower insulitis scores, reduced T-cell proliferation upon stim

249 rved pancreatic insulin content and improved insulitis scores.

250 The presence of beta-cells as well as insulitis several years after diagnosis in children and

251 linical diabetes, age of diabetes onset, and insulitis severity was performed using subphenotype char

252 med for loci affecting clinical diabetes and insulitis severity.

253 nonobese diabetic (NOD) mouse starts with an insulitis stage, wherein a mixed population of leukocyte

254 e preinsulitis phase, but delayed TID at the insulitis stage.

255 umbers and percentage during T cell-mediated insulitis, suggesting that this subset might be involved

256 itatively and quantitatively less aggressive insulitis than do BDC2.5/NOD mice.

257 t 14 and 23 weeks of age exhibited extensive insulitis that progressed with age.

258 ological and immunohistochemical analyses of insulitis, the identification of autoreactive CD8(+) T c

259 lectively, these results suggest that at the insulitis threshold at which CVB4 infection can first ac

260 slet core, resulting in conversion from peri-insulitis to destructive insulitis.

261 Progression from insulitis to diabetes in the nonobese diabetic mouse is

262 ents and murine models, the progression from insulitis to diabetes is neither immediate nor inevitabl

263 Blockade of ICOS rapidly converts early insulitis to diabetes, which disrupts the balance of Tef

264 further analysis of the T cells involved in insulitis to elucidate their role in the etiology of T1D

265 govern the transition from clinically silent insulitis to frank diabetes by cross-presenting autoanti

266 s corresponded with the transition from peri-insulitis to intra-insulitis and occurred in obese A(vy)

267 decrease at the time of conversion from peri-insulitis to invasive insulitis and diabetes.

268 cells, and p546-specific T cells transferred insulitis to NOD.scid mice.

269 -cells that contribute to the progression of insulitis to overt diabetes in NOD mice.

270 frequency (the percent of islets displaying insulitis to total islets), infiltrating leukocyte subty

271 might be a possible autoimmune target and/or insulitis trigger in NOD or congenic mouse strains.

272 distinct stages of islet inflammation, peri-insulitis versus invasive insulitis, were harvested to e

273 Insulitis was absent in diabetes-free recipients and the

274 Suppression of insulitis was associated with an increased frequency, bu

275 type 1 diabetes, we asked whether autoimmune insulitis was associated with changes in the stiffness o

276 Before extended insulitis was established, anti-PRPH B cells preferentia

277 whether PAHSAs were started before or after insulitis was established.

278 spite the alteration in diabetes penetrance, insulitis was evident in T3A-infected mice.

279 Lack of insulitis was found for insulin 1 female homozygous knoc

280 The role of M3 in chemokine blockade during insulitis was further supported by in vitro experiments

281 However, this insulitis was immediately destructive, causing a dramati

282 Furthermore, insulitis was increased in SOCS-1-Tg mice after infectio

283 Importantly, the development of insulitis was markedly absent in the CD18 null mice, sug

284 olygyrus inoculation of NOD mice, pancreatic insulitis was markedly inhibited.

285 This accelerated insulitis was mediated by the loss of plasmacytoid DC (p

286 Insulitis was observed in four of four donors (100%) wit

287 males and males, significantly more advanced insulitis was observed in UBASH3A-deficient than in wild

288 Insulitis was prominent in both groups, but whereas NOD/

289 o depleted mice, the localized regulation of insulitis was restored.

290 Foxp3(+) cells in AhR-induced suppression of insulitis was tested using NOD.Foxp3(DTR) mice, which sh

291 In contrast to insulin 2, diabetes and insulitis were markedly reduced in insulin 1 knockout mi

292 ures such as HLA class I hyperexpression and insulitis were specific for T1D and persisted in a small

293 inflammation, peri-insulitis versus invasive insulitis, were harvested to establish the expression pa

294 -of-function alleles provide protection from insulitis when expressed on the SCID host alone.

295 ted the development of effector function and insulitis whereas Bim-/- clone 4 cells were not autoaggr

296 observed in all type 1 diabetes donors with insulitis, while beta-cell area and mass were significan

297 lymphocytes that manifested as a pancreatic insulitis with beta-islet cell destruction and systemic

298 Loss of Itgb2 or ItgaL prevented insulitis with Itgb2 deficiency conferring complete prot

299 cific Rg T-cells produced variable levels of insulitis, with one TCR producing delayed diabetes.

300 treated diabetes-free mice showed peripheral insulitis, with strong insulin staining.