A novel function of NLRP3 independent of inflammasome as a key transcription factor of IL-33 in epithelial cells of atopic dermatitis

Zheng, Jie; Lu, Yao; Zhou, Yijing; Gu, Xiaoqun; Wang, Can; Bao, Kaifan; Sun, Yang; Hong, Min

doi:10.1038/s41419-021-04159-9

Cited by 40 publications

(35 citation statements)

References 54 publications

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“…Indeed, we observed that cervical dilation and decidual inflammation were both tempered in Nlrp3 -deficient mice independently of CASP-1 activation and maturation of IL-1β, and the baseline expression of cervical tissue genes was different between WT and KO mice. Consistently, the NLRP3 molecule has been previously reported as exhibiting inflammasome-independent functions that include tissue repair ( 96 ), Th2 cell differentiation ( 97 ), restriction of protective early neutrophil responses ( 98 ), and activity as a transcription factor ( 99 ); therefore, it is plausible that such NLRP3-mediated, inflammasome-independent processes could be participating in cervical dilation and decidual inflammation. Moreover, this may also explain why Nlrp3- deficient mice seemed to have low concentrations of total IL-1β in the cervical and decidual tissues upon LPS administration.…”

Section: Discussionmentioning

confidence: 63%

Fetal and maternal NLRP3 signaling is required for preterm labor and birth

Motomura¹,

Romero²,

Galaz³

et al. 2022

JCI Insight

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Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. One of every 4 preterm neonates is born to a mother with intra-amniotic inflammation driven by invading bacteria. However, the molecular mechanisms underlying this hostile immune response remain unclear. Here, we used a translationally relevant model of preterm birth in Nlrp3 -deficient and -sufficient pregnant mice to identify what we believe is a previously unknown dual role for the NLRP3 pathway in the fetal and maternal signaling required for the premature onset of the labor cascade leading to fetal injury and neonatal death. Specifically, the NLRP3 sensor molecule and/or inflammasome is essential for triggering intra-amniotic and decidual inflammation, fetal membrane activation, uterine contractility, and cervical dilation. NLRP3 also regulates the functional status of neutrophils and macrophages in the uterus and decidua, without altering their influx, as well as maternal systemic inflammation. Finally, both embryo transfer experimentation and heterozygous mating systems provided mechanistic evidence showing that NLRP3 signaling in both the fetus and the mother is required for the premature activation of the labor cascade. These data provide insights into the mechanisms of fetal-maternal dialog in the syndrome of preterm labor and indicate that targeting the NLRP3 pathway could prevent adverse perinatal outcomes.

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Section: Discussionmentioning

confidence: 63%

Fetal and maternal NLRP3 signaling is required for preterm labor and birth

Motomura¹,

Romero²,

Galaz³

et al. 2022

JCI Insight

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“…It has been shown that the upregulation of NLRP3 inflammasome is associated with the pathogenesis of chronic dermatitis in the skin of mice [ 37 ]. To determine whether the symptoms of AD were attenuated via the inhibition of the NLRP3 inflammasome, we investigated whether the application of M. concanensis inhibited the NLRP3 inflammasome in DNCB-induced lesional ear tissues.…”

Section: Resultsmentioning

confidence: 99%

Moringa concanensis L. Alleviates DNCB-Induced Atopic Dermatitis-like Symptoms by Inhibiting NLRP3 Inflammasome-Mediated IL-1β in BALB/c Mice

Kim

Mony

et al. 2022

Pharmaceuticals

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Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, dry skin and redness on the face and inside elbows or knees. Most patients with AD are children and youths, but it can also develop in adults. In the therapeutic aspect, treatment with corticosteroids for AD has several side effects, such as weight loss, atrophy and acne. In the current study, we examined the anti-inflammatory effect of Moringa concanensis leaves on HaCaT keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like symptoms in BALB/c mice. We observed that M. concanensis treatment exhibited significant inhibition in the production of inflammatory mediators and proinflammatory cytokines, such as IL-1β, in LPS-induced HaCaT keratinocytes by downregulating the NLRP3 inflammasome activation. Moreover, M. concanensis inhibited the activation of JNK, AP-1 and p65, which resulted in the deformation of NLRP3 in LPS-stimulated HaCaT cells. In mice with DNCB-induced AD-like skin lesions, the administration of M. concanensis ameliorated the clinical symptoms, such as the dermatitis score, thickness of lesional ear skin and TEWL. Furthermore, M. concanensis could attenuate the activation of the immune system, such as reducing the spleen index, concentration of the IgE levels and expression of the NLRP3 inflammasome in ear tissues. Therefore, our results suggest that M. concanensis exerts anti-atopic dermatitis effects by inhibiting the NLRP3 inflammasome-mediated IL-1β.

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“…Interestingly, it is increasingly recognized that members of the intracellular sensor protein NLR family act independently of inflammasomes. 223 , 224 Janowski et al found that NLRC4 in TAMs inhibits melanoma progression by enhancing T cells function. When NLRC4 is defective in mice, macrophages are less able to produce cytokines and chemokines, and subsequently less able to recruit T cells near the tumor, which promotes tumor growth, independent of the inflammasome components ASC and CASP1.…”

Section: Pyroptosis Synergizes Antitumor Immune Responsementioning

confidence: 99%

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Gao

Wang

Zhou

et al. 2022

Sig Transduct Target Ther

396

189

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In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not to ICIs, partly caused by the absence of tumor-infiltrating lymphocytes (TILs), significantly limits the application of ICIs. Converting these immune “cold” tumors into “hot” tumors that may respond to ICIs is an unsolved question in cancer immunotherapy. Since it is a general characteristic of cancers to resist apoptosis, induction of non-apoptotic regulated cell death (RCD) is emerging as a new cancer treatment strategy. Recently, several studies have revealed the interaction between non-apoptotic RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, and necroptosis exhibit synergistic antitumor immune responses while possibly exerting inhibitory effects on antitumor immune responses. Thus, targeted therapies (inducers or inhibitors) against autophagy, ferroptosis, pyroptosis, and necroptosis in combination with immunotherapy may exert potent antitumor activity, even in tumors resistant to ICIs. This review summarizes the multilevel relationship between antitumor immunity and non-apoptotic RCD, including autophagy, ferroptosis, pyroptosis, and necroptosis, and the potential targeting application of non-apoptotic RCD to improve the efficacy of immunotherapy in malignancy.

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A novel function of NLRP3 independent of inflammasome as a key transcription factor of IL-33 in epithelial cells of atopic dermatitis

Cited by 40 publications

References 54 publications

Fetal and maternal NLRP3 signaling is required for preterm labor and birth

Fetal and maternal NLRP3 signaling is required for preterm labor and birth

Moringa concanensis L. Alleviates DNCB-Induced Atopic Dermatitis-like Symptoms by Inhibiting NLRP3 Inflammasome-Mediated IL-1β in BALB/c Mice

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

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