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1 IL-21 also influenced responsiveness to IL-4 because exp
2 IL-21 and IFN-gamma are coexpressed by Tfh cells during
3 IL-21 differentially promoted the expression of the chem
4 IL-21 directly promotes apoptosis of Treg cells and ther
5 IL-21 does not induce Il1b expression in CD4(+) T cells,
6 IL-21 drastically increased the number of IL-10(+) Bregs
7 IL-21 has been implicated in promotion of effector CD4(+
8 IL-21 has been shown to accelerate thymic recovery in mi
9 IL-21 induced STAT1 phosphorylation, and this was augmen
10 IL-21 is a key player of adaptive immunity, with well-es
11 IL-21 is a pleiotropic cytokine produced predominantly b
12 IL-21 promotes B cell and CTL responses in vivo, conferr
13 IL-21 promotes transcription of all miR-29 species throu
14 IL-21 was a critical negative regulator of IgE responses
15 IL-21, a Tfh cell-derived cytokine, provides instruction
16 IL-21-induced IL-1beta processing in cDCs does not requi
17 IL-21-mediated cMyc upregulation is only observed in IL-
19 onocytes were treated with histamine, IL-17, IL-21 and IL-22, and a H4R antagonist (JNJ7777120), the
20 iotic regimens significantly reduced IL-17A, IL-21, IL-22 and IFN-gamma mRNA levels in the terminal i
21 Inflammatory cells and IL-17A(+), IL-17F(+), IL-21(+), IL-22(+), and IL-23(+) cells were examined by
22 cytokines (interleukin-17A [IL-17A], IL-17F, IL-21, IL-22, and IL-26) in regulating the immune respon
23 h induction of intracellular interleukin 21 (IL-21) and inducible costimulator (ICOS) post vaccinatio
25 o mutating B cells, secreted interleukin 21 (IL-21), induced expression of the transcription factor B
26 0-targeted therapy, we fused interleukin 21 (IL-21), which induces direct lymphoma cytotoxicity and a
28 nt on CD4(+) T cell help via interleukin-21 (IL-21) and that exploitation of this developmental pathw
30 une cell-mediated effects of interleukin-21 (IL-21) in mantle cell lymphoma (MCL), providing a precli
32 maintained by T-cell-derived interleukin-21 (IL-21), and promoted repeated rounds of divisions of sel
33 se SOX11 expression, whereas interleukin-21 (IL-21)-induced STAT3 activation or overexpression of the
34 all subset of gp120-specific interleukin-21 (IL-21)-secreting CXCR5(+) CD4(+) T cells were significan
36 l a relationship among TLR engagement, IL-4, IL-21, and IFN-gamma that regulates T-bet expression in
38 expression of IL-17, TNF-alpha, IL-6, IL-4, IL-21, TGF-beta1 and IFN-gamma were significantly increa
39 thermore, IL-6-stimulated production of IL-4/IL-21 through c-Maf induction is responsible for impaire
40 TAT3 and STAT1 activation profiles for IL-6, IL-21, and IL-27, as well as for cytokine pairs over tim
42 ent in the presence of interleukin-7 (IL-7), IL-21, and the glycogen synthase-3beta inhibitor TWS119,
46 LDH inhibition did not significantly affect IL-21-induced metabolism but caused major transcriptomic
49 the dual functional ability of the alphaCD20-IL-21 fusokine to induce direct apoptosis and activate i
51 dysfunctional Ag.pTfh cells with an altered IL-21/IL-2 axis contribute to inadequate vaccine respons
56 im of this study is to test the effect of an IL-21 receptor (IL-21R) blocking antibody on the early p
57 ), IL-4(+) (V6, P = .003; V8, P = .004), and IL-21(+) (V6, P = .003; V8, P = .002) follicular helper
61 gamma and oncostatin M, as well as IL-15 and IL-21, activity and resulted in clinical and histologic
65 nd higher numbers (P < .01) of IL-17F(+) and IL-21(+) cells in nasal biopsies were observed in SAs co
66 5) of neutrophils, IL-17A(+), IL-17F(+), and IL-21(+) cells in bronchial biopsies and higher numbers
68 , soluble CD40L in combination with IL-2 and IL-21 induces these activities in both memory and naive
69 at soluble BAFF in combination with IL-2 and IL-21 is a T cell contact-independent inducer of human B
71 and extending these findings, TNF, IL-2, and IL-21 also synergistically triggered the proliferation o
73 ion that the soluble factors BAFF, IL-2, and IL-21 induce memory and DN B cell activation and differe
74 n Ag that induced type 1 immunity), IL-4 and IL-21 were coproduced by individual Tfh cells, revealing
77 ed interferon-gamma, interleukin (IL)-4, and IL-21 cytokines; and NKT cell-derived perforin and granz
79 Moreover, rfhSP-D inhibited CD40L/IL-4- and IL-21-mediated IgE production (77.12%; P = 0.02) by B ce
80 IL-35 inhibited CD40 ligand-, IL-4-, and IL-21-mediated IgE production by B cells (P = .015), all
81 (T(FH))-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of p
82 hibited the production of autocrine IL-6 and IL-21 in 2D2 T cells, which in turn reduced their Th17 d
83 on was decreased in the presence of IL-6 and IL-21, and to a lesser extent by IL-4 and TNF-alpha.
84 Tfh cells following interleukin-6 (IL-6) and IL-21 stimulation, and viral DNA is detectable in fully
85 ar brake that blocks the autocrine IL-6- and IL-21-induced Th17 differentiation pathways in autoreact
86 analysis revealed enhancements in IL-6- and IL-21-induced Th17 differentiation pathways in these T c
87 ven ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and
88 response to key T cell signals like CD40 and IL-21 and that it regulated GC formation and maintenance
92 ated both the number of IL-21(+) T cells and IL-21 production, suggesting a feedback loop in tolerant
93 gnate interaction between Tfh , B cells, and IL-21 drives B cells to proliferate and differentiate in
95 e in Tfr cells, inhibits CD25 expression and IL-21-mediated inhibition of CD25 is Bcl-6 dependent.
97 TH1 and TFH effector cytokines IFN-gamma and IL-21 and the TFH marker CXCR5, demonstrating that the c
100 ial infection require CD4(+) T cell help and IL-21 signaling for their development, but the exact T c
105 ifferentiation depends on normal p-STAT3 and IL-21 production to suppress p-STAT1 activation and T-be
106 r elements bound by IL-2-activated STAT5 and IL-21-activated STAT3 in T cells and identified Il2ra as
108 of lupus-prone B6.Sle1.Yaa mice with an anti-IL-21 blocking Ab reduced titers of autoantibodies, dela
109 reduced Bcl6 and PD-1 expression as well as IL-21 production by T(FH) cells, preventing proper spati
110 These results reveal an interplay between IL-21 and type I IFN in the innate immune response to MR
112 'NKF' through overexpressing membrane bound IL-21 that is capable of inducing robust and sustained p
113 anistic studies revealed that membrane-bound IL-21 leads to an activation of a STAT3/c-Myc pathway an
115 esenting cells in the presence of IL-21, but IL-21 did impact the ability of DCs to induce antigen-sp
118 irectly by RNA interference or indirectly by IL-21 treatment induced toxicity in SOX11(+) MCL cells.
120 morigenic effects were mediated primarily by IL-21 and CD40 signaling, leading to the upregulation of
121 ibition of IgE class switch recombination by IL-21 was attenuated by CD40 signaling, whereas IgG1 cla
124 proliferation similarly differed, with CD40L/IL-21 inducing proliferation of most memory and naive B
125 uired alongside STAT4 to coordinate Tfh cell IL-21 and IFN-gamma production and for promotion of the
126 r to CD4(+) T follicular helper (Tfh) cells, IL-21-producing CD8(+) T cells generated in the presence
127 chultz et al. (2016) report that circulating IL-21-producing CD4(+) T cells are phenotypically, trans
128 ssive accumulation of Tfh cells coexpressing IL-21 and IFN-gamma, and suppressed their production of
129 wever, Th17-related cytokine concentrations (IL-21, IL-1beta, TNF-alpha, IFN-gamma) and CCR5+HLA-DR+C
130 under homeostatic or lymphopenic conditions IL-21 acts directly on CD8 T cells to favor the accumula
131 B cell and CTL responses in vivo, conferring IL-21 with a role in both humoral and cellular responses
132 eless, using an expansion mixture containing IL-21, anti-BCR, CpG oligodeoxynucleotide, CD40L, and IL
134 cell sorter, to polarize IL-21(+)CXCL13(+) (IL-21-positive and C-X-C chemokine ligand type 13-positi
135 in high expression of the signature cytokine IL-21, the coinhibitory receptor TIGIT and the transcrip
137 expression of costimulatory proteins on DCs, IL-21 reduced the expression of CD40 in the presence of
139 antibodies, indicating that Tfh cell-derived IL-21 is critical for pathological B cell cues in lupus.
140 on in normal T(H)9 cultures diminished early IL-21 induction and late IL-9 production, whereas exogen
142 te infection, is associated with an elevated IL-21(+) CD4 T subset, and these cells bear a phenotypic
143 of autoreactive CD4(+) T cells and elevated IL-21 and IFN-gamma production, associated with a higher
145 atients display CD4(+) T cells with enhanced IL-21 expression and high in vivo frequencies of regulat
147 and late IL-9 production, whereas exogenous IL-21 enhanced T(H)9 differentiation, even with STAT3 in
148 GC response evolved, TFH cells extinguished IL-21 production and switched to IL-4 production, showed
151 ese results demonstrate a novel function for IL-21 in tuning NK and CD4(+) T cell interactions promot
154 identify a previously unappreciated role for IL-21 in EAE and reveal that IL-21-mediated signaling su
155 s study reveals a context-dependent role for IL-21 in sustaining effector phenotype CD8 T cells and i
156 this report demonstrates a critical role for IL-21 in the generation of a primary effector CD8 T cell
158 ssociated with early induction of functional IL-21-secreting circumsporozoite (CSP)-specific pTfh cel
162 and follicular Th cell paradigms to generate IL-21 and IL-17A, which drive pathogenic germinal center
163 l cytokine profile (IL-13(hi)IL-4(hi)IL-5(hi)IL-21(lo)) and coexpress the transcription factors BCL6
164 e identified a subpopulation of GFP(+), high IL-21 producing Tfh cells present only in Peyer's Patche
166 like CD4 T cell-driven B cell hyperactivity, IL-21 signaling on Ag-specific donor CD8 T cells is crit
168 healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-alpha, IL-6 or BAFF induces miR-155 and
170 This review will focus on recent advances in IL-21 biology that have highlighted its critical role in
171 athways and increased neuronal cell death in IL-21 receptor-deficient (IL-21R-deficient) mice compare
180 rail-deficient CD8(+) T cells have increased IL-21 receptor (IL-21R) expression and hyperresponsivene
182 sitive) OX-40L-expressing cDC2s that induced IL-21(+) Tfh-like cells, suggesting an involvement of th
183 rom chronic inflammation, H. pylori-infected IL-21(-/-) mice exhibited limited Th1 and Th17 responses
185 t, during per-oral microsporidial infection, IL-21 was critical for the generation of an optimal effe
186 Here the authors show Grail also limits IL-21 receptor expression and function in CD8(+) T cells
188 stered intra-tracheally into wild-type mice, IL-21 induced granzymes and augmented clearance of pulmo
189 g a mixed bone marrow chimeric animal model, IL-21 seems to be involved as early as the double-negati
195 lating T(FH) cells produced large amounts of IL-21 upon stimulation with donor antigen and induced B
196 These findings demonstrate that blockade of IL-21 signaling can delay allograft rejection in a human
199 mechanistic insight into the contribution of IL-21 to the pathogenesis of murine lupus, while reveali
201 for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic str
202 ceptor-deficient mice to study the effect of IL-21 on T-cell responses in models of asthma and coliti
206 This correlated with increased expression of IL-21 and CD40L in Tfh cells from Sfpi1(lck-/-) mice com
207 nd IL-12 controlled respective expression of IL-21 and IFN-gamma, with IL-21 being key for humoral im
208 edly STAT3, promotes increased expression of IL-21 and the T(FH) lineage-defining transcription facto
209 IgA expression associated with expression of IL-21, which was very potent to activate immunoglobulin
214 17 cytokines but did reveal higher levels of IL-21, the main cytokine secreted by CD4 T follicular he
215 r differentiation of Th17 cells, the loss of IL-21 or IL-21 receptor (IL-21R) does not protect mice f
217 ents positively regulated both the number of IL-21(+) T cells and IL-21 production, suggesting a feed
219 antigen-presenting cells in the presence of IL-21, but IL-21 did impact the ability of DCs to induce
221 these kinases in TFH inhibits production of IL-21, a cytokine crucial for class-switched B cell anti
224 elated genes, indicating a potential role of IL-21 in memory IgA(+) B cell responses in the intestine
231 ew our current understanding of the roles of IL-21 in the generation of phenotypically distinct CD4 a
232 ) T-bet(+) B cells via the dual secretion of IL-21 and IFN-gamma in a CD40/CD40L-dependent manner.
233 strating the KD025 inhibits the secretion of IL-21, IL-17, and interferon gamma along with decreasing
234 ar helper T cells were the primary source of IL-21 that inhibited IgE responses by directly engaging
236 ptomic changes, including the suppression of IL-21-induced exhaustion markers LAG3, PD1, 2B4, and TIM
238 s-specific CD8 T cells remained dependent on IL-21 for optimal accumulation in lymphopenic environmen
239 ally, GzmB(+) B-cell number was dependent on IL-21 production, and B cells from tolerant recipients b
240 equire caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s
241 ntiation of Th17 cells, the loss of IL-21 or IL-21 receptor (IL-21R) does not protect mice from activ
242 t not the pro-inflammatory cytokines IL-6 or IL-21, is required via STAT3 activation to up-regulate B
244 pha, and compared with activators CD40L plus IL-21, to identify differentially responsive cell popula
245 orescence-activated cell sorter, to polarize IL-21(+)CXCL13(+) (IL-21-positive and C-X-C chemokine li
247 tion of these Tc2 cells in the lung requires IL-21, and bleomycin treated IL-21- and IL-21R-deficient
248 These results demonstrate lineage-restricted IL-21-induced IL-1beta via a non-canonical pathway and p
249 Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD4
250 the frequency of total and SIV Env-specific IL-21(+) TFH cells and total germinal center B cells, th
251 n this study, we quantified SIV Env-specific IL-21-producing TFH cells for the first time, to our kno
254 t as critical as IL-7, based on our studies, IL-21 plays an important complementary role in thymic T
256 ma, IL-2, anti-Ig and TLR7/8 ligand and that IL-21 dependent ASC formation is significantly enhanced
260 In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development,
261 In this study, we provide evidence that IL-21, a cytokine produced during chronic inflammation o
267 osal infection, we previously published that IL-21 is required for the development of gastritis in re
268 ciated role for IL-21 in EAE and reveal that IL-21-mediated signaling supports generation and stabili
269 +) and Il21r(-/-) CD4(+) cells, we show that IL-21 directly inhibited expansion of differentiated Tre
275 bited IgE responses by directly engaging the IL-21 receptor on B cells and triggering STAT3-dependent
276 sion in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infe
278 ic, as stronger defects were observed in the IL-21-deficient compartment from the bone marrow chimeri
279 th follicular and blood Tfh cells and of the IL-21/IL-21R system in the context of allergic disorders
281 L-21R) expression and hyperresponsiveness to IL-21 signalling as Grail promotes IL-21R ubiquitination
284 e lung requires IL-21, and bleomycin treated IL-21- and IL-21R-deficient mice develop inflammation bu
287 we demonstrate that CD4 help is provided via IL-21 production, a common gamma-chain cytokine closely
288 basal MRSA clearance was also enhanced when IL-21 signaling was blocked, both in Il21r KO mice and i
289 peribronchiolar LFs from severe COPD, where IL-21-producing T cells are present, and presumably repr
290 genase (LDH) and lactate production, whereas IL-21 maintained a metabolically quiescent state depende
291 are poorly effective against tumors, whereas IL-21 promotes stem cell memory T cells (T(SCM)) and ant
292 sought to understand the mechanisms by which IL-21 controls effector CD4(+) cell responses and Treg c
293 These findings identify a mechanism by which IL-21 reinforces humoral immunity by restricting Tfr cel
294 those reported for viral infections in which IL-21 has been primarily associated with the generation
296 induced by CpG or CD40L in combination with IL-21, but not BCR stimulation, suggesting the importanc
299 y secretion, whereas CD40 costimulation with IL-21 or IFN-gamma promotes a T-bet+ B cell phenotype.
301 atment of DBA/2J-->F1 chronic GVHD mice with IL-21 strongly promoted donor CD8 T cell expansion and r
302 -2, IFN-gamma, and TNF-alpha production with IL-21 in CD4 or CD107a, granzyme B and perforin in CD8 T