_applied sciences_  
_Systematic Review_  
**Mechanism behind the Upregulation of Proteins Associated with the NLRP3 Inflammasome in Periodontitis and Their Role in the Immune Response in Diabetes--A Systematic Review**  
[PERSON] \({}^{1}\)\({}^{\copyright}\), [PERSON] \({}^{2}\), [PERSON] \({}^{3}\), [PERSON] \({}^{4}\), [PERSON] \({}^{5}\), [PERSON] \({}^{6}\)\({}^{\copyright}\) and [PERSON] \({}^{7,*}\)\({}^{\copyright}\)  
\({}^{1}\) Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio, 66100 Chieti, Italy; [EMAIL_ADDRESS]  
\({}^{2}\) Burn Unit, Ospedale Ferrino, 72100 Brindisi, Italy; [EMAIL_ADDRESS]  
\({}^{3}\) Freelance Researcher, 70121 Bari, Italy; [EMAIL_ADDRESS]  
\({}^{4}\) Department of Biomedical Sciences, Humanits University, [PERSON] 4, 20072 Pieve Emanuele, Italy; [EMAIL_ADDRESS]  
\({}^{5}\) Department of Basic Medical Sciences, Neurosciences and Sense Organs, \"Aldo Moro\" University of Bari, 70121 Bari, Italy; [EMAIL_ADDRESS]  
\({}^{6}\) Department of General Surgery and Surgical-Medical Specialities, School of Dentistry, University of Catania, 95124 Catania, Italy; [EMAIL_ADDRESS]  
\({}^{7}\) Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy  
\({}^{*}\) Correspondence: [EMAIL_ADDRESS]; Tel: +39-3477619817  
**Abstract: Background: The molecular crosstalk between periodontitis and diabetes is well established. The role of the NLRP3 inflammasome, a multicomponent inflammatory machinery, is an emerging field of research on the relationship between these two communicable diseases. Recent advances are revealing further molecular details regarding the biological function and the mechanism behind the NLRP3 inflammasome dysregulation and highlighting an unexpected role for the caspase-1 in immune homeostasis. We aimed to understand which metabolic checkpoints are involved in contributing to and instigating the relationship between periodontitis and diabetes. We tried to explore the involvement of the NLRP3 in regulating the cytokine-chemokines profile and discussed the potential synergism in these mechanisms when these two diseases coexist in the same patient. Methods: A literature search was carried out in the electronic databases (MEDLINE, EMBASE, and Cochrane Library) for relevant studies from inception until January 2022 for trials and cohort studies that investigated the activation and regulation mechanism of the NLRP3 inflammasome in patients with periodontitis and type two diabetes. Two investigators independently extracted data. The data quality assessment was rated by the Joanna Briggs Institute (JBI). Results: from twenty-six references identified, three studies (two case-control and one cross-sectional) met the inclusion criteria. Analysis of periodontal tissue samples in diabetic individuals exhibited significant overexpression of the NLRP3 inflammasome when compared with healthy controls. Conclusions: there is insufficient evidence to sustain the involvement of the upregulation of genes and proteins involved in the activation of NLRP3 inflammasome components in patients with periodontitis and diabetes.**  
**Keywords: periodontitis; diabetes; NLRP3 inflammasome; immune response**