NLRP1 acts as a negative regulator of Th17 cell programming in mice and humans with autoimmune diabetes

Costa, Frederico R. C.; Leite, Jefferson Antônio; Rassi, Diane Meyre; Silva, Josiane F.; Elias-Oliveira, Jefferson; Guimarães, Jhefferson Barbosa; Foss‐Freitas, Maria Cristina; Câmara, Niels Olsen Saraiva; Pontillo, Alessandra; Tostes, Rita C.; Silva, João; Carlos, Daniela

doi:10.1016/j.celrep.2021.109176

Cited by 15 publications

(7 citation statements)

References 44 publications

(58 reference statements)

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“…These data indicate that NLRP1 played a protective role in high-fat-induced metabolic syndrome ( Figure 3 ). In addition, NLRP1 has a protective effect in type 1 diabetes ( 25 ). After 10 days of streptozotocin injection, blood glucose levels in NLRP1 -/- mice were higher than that of WT mice, and inflammatory infiltration in pancreatic islets was increased.…”

Section: Role Of the Inflammasome In Insulin Resistancementioning

confidence: 99%

Role of the inflammasome in insulin resistance and type 2 diabetes mellitus

Qian

et al. 2023

Front. Immunol.

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The inflammasome is a protein complex composed of a variety of proteins in cells and which participates in the innate immune response of the body. It can be activated by upstream signal regulation and plays an important role in pyroptosis, apoptosis, inflammation, tumor regulation, etc. In recent years, the number of metabolic syndrome patients with insulin resistance (IR) has increased year by year, and the inflammasome is closely related to the occurrence and development of metabolic diseases. The inflammasome can directly or indirectly affect conduction of the insulin signaling pathway, involvement the occurrence of IR and type 2 diabetes mellitus (T2DM). Moreover, various therapeutic agents also work through the inflammasome to treat with diabetes. This review focuses on the role of inflammasome on IR and T2DM, pointing out the association and utility value. Briefly, we have discussed the main inflammasomes, including NLRP1, NLRP3, NLRC4, NLRP6 and AIM2, as well as their structure, activation and regulation in IR were described in detail. Finally, we discussed the current therapeutic options-associated with inflammasome for the treatment of T2DM. Specially, the NLRP3-related therapeutic agents and options are widely developed. In summary, this article reviews the role of and research progress on the inflammasome in IR and T2DM.

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Section: Role Of the Inflammasome In Insulin Resistancementioning

confidence: 99%

Role of the inflammasome in insulin resistance and type 2 diabetes mellitus

Qian

et al. 2023

Front. Immunol.

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“…It is important to note that the association resulted significant in all the three steps of analysis, even when well-known risk variables, age, sex, hypertension, and diabetes, have been included in the multivariate analysis. As NLRP1 has been previously associated to Addison disease [ 22 ], and type-1 diabetes [ 23 , 24 ], we performed an association analysis using diabetes as main variable, instead of a covariate, however, at least in our cohort, none of the studied SNVs resulted associated to diabetes. The same result was obtained when hypertension was used as main variable, finally excluding a possible effect of rs12150220 on these two conditions in our cohort, and emphasizing the robustness of the main association analysis.…”

Section: Discussionmentioning

confidence: 99%

“…As NLRP1 has been previously associated to Addison disease [19], and type-1 diabetes [20][21] we performed an association analysis using diabetes as main variable, instead of a covariate, however, at least in our cohort, none of the studied SNVs resulted associated to diabetes. The same result was obtained when was used as main variable, nally excluding a possible effect of rs12150220 on these two conditions in our cohort.…”

Section: Discussionmentioning

confidence: 99%

A common variant close to the “tripwire” linker region of NLRP1 contributes to severe COVID-19

et al. 2022

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Objective and design The heterogeneity of response to SARS-CoV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome-related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stands out as a good novel candidate as severity factor for COVID-19 disease. Methods To address this question, we performed an association study of NLRP1 , DPP9 , CARD8 , IL1B , and IL18 single nucleotide variants (SNVs) in a cohort of 945 COVID-19 patients. Results The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to COVID-19 severity, which could contribute to the excessive cytokine release reported in severe cases. Conclusion Inflammasome genetic background contributes to individual response to SARS-CoV-2. Supplementary Information The online version contains supplementary material available at 10.1007/s00011-022-01670-3.

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“…The multiple effects of NLRP1 and NLRP3 are closely related to various human diseases associated with dysfunctional immunoregulation, including autoimmune diseases [12], asthma [13], psoriasis [14], lupus nephritis [15], and Alzheimer's disease [16], and have also been reported to play crucial roles in tumor progression, prognosis, and treatment response [17][18][19]. However, due to the tissue-dependent or cell-dependent roles of inflammasomes in tumorigenesis, the expression levels of inflammasome-related genes vary, and these genes play various roles in different cancers [20].…”

Section: Introductionmentioning

confidence: 99%

The prognostic value of NLRP1/NLRP3 and its relationship with immune infiltration in human gastric cancer

Wang

Yang

et al. 2022

Aging

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Background: Inflammasomes are related to tumorigenesis and immune-regulation. Here, we investigated the prognostic value of the NLR family pyrin domain containing (NLRP) 1/NLRP3 inflammasome and its potential mechanisms in immune-regulation in gastric cancer (GC). Methods: We analyzed the differential expression of NLRP1/NLRP3 between tumor and normal tissues using the Oncomine and Tumor Immune Estimate Resource (TIMER) databases. Immunohistochemistry and western blotting were used to detect NLRP1/NLRP3 protein expression in GC tissues. Correlations between NLRP1/NLRP3 expression levels and patient survival were analyzed using Kaplan-Meier survival curves. The relationships of NLRP1/NLRP3 expression and tumor-infiltrating immune cells/marker genes were assessed using the TIMER database. NLRP1/NLRP3 and immune checkpoint gene correlations were verified by singlegene co-expression analyses, and tumor immune-related pathways involving NLRP1/NLRP3 were analyzed using gene set enrichment analysis (GSEA). Results: Elevated NLRP1/NLRP3 expression was significantly correlated with lymph node metastasis, poor survival, immune-infiltrating cell abundances, and immune cell markers. NLRP3 showed stronger correlations with immune infiltration and the prognosis of gastric cancer. NLRP1 and NLRP3 might be involved in the same tumor immune-related pathways. Thus, high NLRP1/NLRP3 expression promotes immune cell infiltration and poor prognosis in GC. NLRP1/NLRP3, particularly NLRP3, may have important roles in immune infiltration and may serve as a prognostic biomarker for GC. Conclusions: NLRP1/NLRP3, particularly NLRP3, may have important roles in immune infiltration and may serve as a prognostic biomarker for GC.

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NLRP1 acts as a negative regulator of Th17 cell programming in mice and humans with autoimmune diabetes

Cited by 15 publications

References 44 publications

Role of the inflammasome in insulin resistance and type 2 diabetes mellitus

Role of the inflammasome in insulin resistance and type 2 diabetes mellitus

A common variant close to the “tripwire” linker region of NLRP1 contributes to severe COVID-19

The prognostic value of NLRP1/NLRP3 and its relationship with immune infiltration in human gastric cancer

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