Effects of Candidalysin Derived from Candida albicans on the Expression of Pro-Inflammatory Mediators in Human Gingival Fibroblasts.

Candida albicans (Ca) is frequently detected in the peri-implant sulcus with peri-implantitis, a major postoperative complication after oral implant therapy. However, the involvement of Ca in the pathogenesis of peri-implantitis remains unclear. In this study, we aimed to clarify Ca prevalence in the peri-implant sulcus and investigated the effects of candidalysin (Clys), a toxin produced by Ca, on human gingival fibroblasts (HGFs). Peri-implant crevicular fluid (PICF) was cultured using CHROMagar and Ca colonization rate and colony numbers were calculated. The levels of interleukin (IL)-1ß and soluble IL-6 receptor (sIL-6R) in PICF were quantified by enzyme-linked immunosorbent assay (ELISA). Pro-inflammatory mediator production and intracellular signaling pathway (MAPK) activation in HGFs were measured by ELISA and Western blotting, respectively. The Ca colonization rate and the average number of colonies in the peri-implantitis group tended to be higher than those in the healthy group. IL-1ß and sIL-6R levels in the PICF were significantly higher in the peri-implantitis group than in the healthy group. Clys significantly induced IL-6 and pro-matrix metalloproteinase (MMP)-1 productions in HGFs, and co-stimulation with Clys and sIL-6R increased IL-6, pro-MMP-1, and IL-8 production levels in HGFs compared with Clys stimulation alone. These findings suggest that Clys from Ca plays a role in the pathogenesis of peri-implantitis by inducing pro-inflammatory mediators.

Current development status of additive manufacturing technologies for fabricating removable partial denture frameworks: a literature review.

AIM: The aim of the present study was to review the current development status of additive manufacturing (AM) technology for fabricating frameworks for removable partial dentures (RPDs) considering fit accuracy, surface condition, and mechanical strength. METHODS: A search of the databases of MEDLINE, Cochrane Library, and Science Direct was conducted using definite keywords ("removable partial denture" or "framework" or "dental prosthesis design") and ("additive manufacturing technology" or "rapid prototyping" or "3D-printing"). RESULT: A total of 23 articles were selected according to certain inclusion criteria. The direct AM techniques were applied to manufacture metal RPD frameworks consisting of selective laser melting (SLM), selective laser sintering (SLS), and metal binder jetting (MBJ). The SLM technique showed a good surface and mechanical strength, but low accuracy. The SLS technique showed higher accuracy than indirect AM, but further studies are required. The MBJ technique showed lower accuracy and a rougher surface than the conventional method. CONCLUSION: AM techniques can produce RPD frameworks within the acceptable range for clinical practice; however, more clinical studies are needed.

Assessment of potential clinical cascade between oral hypofunction and physical frailty: Covariance structure analysis in a cross-sectional study.

No report has yet examined the impact of oral hypofunction on physical frailty in relation to intra-relationships of physical frailty assessment items. The purpose of this study was to verify the potential of a clinical cascade between oral hypofunction and physical frailty, and especially to support the hypothesis that the influence of oral hypofunction on physical frailty is greater than the intra-relationships among elements of physical frailty and that sex differences significantly affect these relationships. The participants were 272 older adults (101 men and 171 women; mean age 75.1 ± 7.5 years). Maximum occlusal force (MOF) and oral dryness (OD), as indicators of oral hypofunction, and grip strength (GS) and walking speed (WS), as indicators of physical frailty, were measured. Mutual relationship of four variables was verified using covariance structure analysis. In men, three paths from MOF to WS and GS and from WS to GS were confirmed, and those from MOF to WS and from WS to GS were found to be significant (P < .01). In women, three paths from MOF to WS and GS and from WS to GS were also confirmed, as with the men, and those from MOF to WS and from MOF to GS were found to be significant (P < .01). Model adaptability was shown to be good for both men and women. The results suggest our hypothesis was verified, and it is expected that the early detection of oral hypofunction, that is MOF, may be important for assessing physical frailty, especially in women.

Prefrontal cortex activity induced by periodontal afferent inputs downregulates occlusal force.

The prefrontal cortex (PFC) plays an important role in several cognitive functions, such as planning, decision making, and social behavior. We previously reported that periodontal sensory input significantly increases PFC activity during the motor task of maintaining occlusal (biting) force. However, the relationships between periodontal sensation, PFC activity, and the performance of motor tasks have not been evaluated in detail. Therefore, using functional near-infrared spectroscopy, we investigated PFC activity by monitoring changes in cerebral blood flow (CBF) to specific areas of the PFC that corresponded to changes in occlusal force generated during four different biting tasks: (1) occlusion with the central incisor with an interocclusal distance of 5 mm (BI-5 mm); or (2) 10 mm (BI-10 mm); (3) occlusion with the first molars with an interocclusal distance of 5 mm (BM-5 mm), or (4) 10 mm (BM-10 mm). Occlusion of molars generated increased PFC regional CBF as the interocclusal distance decreased (BM-10 mm vs BM-5 mm). No significant differences in CBF during occlusion of incisors were found when comparing 5 mm and 10 mm intercostal distances (BI-5 mm vs BI-10 mm). The mean occlusal force generated by BM-5 mm occlusion was significantly lower than that generated by BM-10 mm occlusion. Taken together, our results suggest that the PFC decreases efferent signaling to motor units, to reduce occlusal force generated when periodontal sensation, which is greater when the interocclusal distance is reduced, is primarily responsible for maintaining occlusal force in the absence of sensations from the temporomandibular joint and muscle spindles.

Antifungal and Mechanical Properties of Tissue Conditioner Containing Plant-Derived Component: An In Vitro Study.

PURPOSE: To evaluate the antifungal activity and mechanical properties of a novel antifungal tissue conditioner containing Juncus powder. MATERIALS AND METHODS: Juncus powder was mixed with GC tissue conditioner at concentrations of 2.5%, 5.0%, and 10.0% by mass. The cylindrical specimens of Juncus-mixed tissue conditioner (dimensions: 10 mm in diameter and 2 and 6 mm in height for antimicrobial and mechanical tests, respectively) were prepared. The specimens placed on the bottom of the 24-well tissue culture plate were cultured with Candida albicans CAD1 for 2 and 4 days. The proliferation of the C. albicans in the wells was determined by measuring the optical density of fungal culture, and the surface of the specimens were also observed by scanning electron microscopy (SEM). To assess the mechanical properties of the specimens, the fluidity and hardness of Juncus-mixed tissue conditioner were measured using the methods certified according to ISO 10139-1. RESULTS: Juncus-mixed tissue conditioner significantly exhibited growth inhibitory effect in a Juncus concentration-dependent manner after both 2- and 4- day cultures. SEM observation showed that the amount of C. albicans on Juncus-mixed specimens drastically decreased, and biofilm formation was markedly inhibited. Moreover, both mechanical properties were found to be within the ranges regulated and specified by ISO. CONCLUSION: These findings demonstrated that the tissue conditioner including Juncus powder has a significant growth inhibitory effect against C. albicans, and it is suggested that the application of Juncus-mixed tissue conditioner may prevent denture stomatitis and oral candidiasis in denture wearers.

Development of a digital impression procedure using photogrammetry for complete denture fabrication.

OBJECTIVES: We developed an innovative procedure for digitizing maxillary edentulous residual ridges with a photogrammetric system capable of estimating three-dimensional (3D) digital forms from multiple two-dimensional (2D) digital images. The aim of this study was to validate the effectiveness of the photogrammetric system. MATERIALS AND METHODS: Impressions of the maxillary residual ridges of five edentulous patients were taken with four kinds of procedures: three conventional impression procedures and the photogrammetric system. Plaster models were fabricated from conventional impressions and digitized with a 3D scanner. Two 3D forms out of four forms were superimposed with 3D inspection software, and differences were evaluated using a least squares best fit algorithm. RESULTS: The in vitro experiment suggested that better imaging conditions were in the horizontal range of ± 15 degrees and at a vertical angle of 45 degrees. The mean difference between the photogrammetric image (Form A) and the image taken from conventional preliminarily impression (Form C) was 0.52 ± 0.22 mm. The mean difference between the image taken of final impression through a special tray (Form B) and Form C was 0.26 ± 0.06 mm. The mean difference between the image taken from conventional final impression (Form D) and Form C was 0.25 ± 0.07 mm. The difference between Forms A and C was significantly larger than the differences between Forms B and C and between Forms D and C. CONCLUSION: The results of this study suggest that obtaining digital impressions of edentulous residual ridges using a photogrammetric system is feasible and available for clinical use.

Part-Digitizing System of Impression and Interocclusal Record for Complete Denture Fabrication.

Few studies have reported the application of digital technology to removable dentures, particularly for the process of impression and interocclusal recording for complete denture fabrication. This article describes a part-digitizing system of impression and interocclusal records for complete denture fabrication. The denture foundation area in an edentulous mouth, including the border areas and residual ridge, is outlined by tracing the surfaces with a 3-D pen-type digitizer. Specialized trays for final impressions and interocclusal records were generated using computer-aided design and manufactured using the digital data. Final impression and interocclusal records were carried out using these specialized trays. The computer-aided method using preliminary digital impressions and specialized trays would be feasible for clinical use for complete denture fabrication.

Influence of matrix attachment installation load on movement and resultant forces in implant overdentures.

PURPOSE: This in vitro study investigated the effect of attachment installation conditions on the load transfer and denture movements of implant overdentures, and aims to clarify the differences among the three types of attachments, namely ball, Locator, and magnet attachments. MATERIALS AND METHODS: Three types of attachments, namely ball, Locator, and magnetic attachments were used. An acrylic resin mandibular edentulous model with two implants placed in the bilateral canine regions and removable overdenture were prepared. The two implants and bilateral molar ridges were connected to three-axis load-cell transducers, and a universal testing machine was used to apply a 50 N vertical force to each site of the occlusal table in the first molar region. The denture movement was measured using a G(2) motion sensor. Three installation conditions, namely, the application of 0, 50, and 100 N loads were used to install each attachment on the denture base. The load transfer and denture movement were then evaluated. RESULTS: The resultant force decreased with increasing installation load for all attachments. In particular, the resultant force on implants on the loading side of the Locator attachment significantly decreased when the installation load was increased from 0 to 50 N, and that for magnetic attachment significantly decreased when the installation load was increased from 50 to 100 N. For the residual ridges on the loading side, the direction of the forces for all attachments changed to downward with increasing installation load. Furthermore, the yaw Euler angle increased with increasing installation load for the magnetic attachment. CONCLUSIONS: Subject to the limitations of this study, the use of any installation load greater than 0 N is recommended for the installation of ball and Locator attachments on a denture base. Regarding magnetic attachments, our results also recommend installation on a denture base using any installation load greater than 0 N, and suggest that the resultant force acting on the implant can be decreased by increasing the installation load; however, a large installation load of 100 N should be avoided when installing the attachment on the denture base to avoid increasing the denture movement.

Do sensation differences exist between dental implants and natural teeth?: a meta-analysis.

OBJECTIVE: The purpose of this systematic review was to survey evidence pertaining to the sensation differences between natural teeth and osseointegrated dental implants. MATERIAL AND METHODS: Using the MEDLINE (online PubMed) database, Cochrane Library, and Scientific Citation index, we performed a systematic search of articles. We used the following search terms: "perception or sensation and dental implant." The systematic review of the extracted articles was performed to see the sensation differences between natural teeth and dental implants. RESULTS: A total of six studies on oral sensation, "tactile sensibility," and "thickness discrimination" were included in the meta-analysis. As to the "tactile sensibility", all studies indicated the threshold levels of the implants were about 4-20 times higher than that of natural teeth. The tactile sensibility of an implant was significantly higher than that of a natural tooth, with an standardized mean difference (SMD) of 8.3619 (95% CI, 6.3920-10.3317) and a P < 0.0001. As to the "thickness discrimination", all studies indicated the threshold levels of implants were about 1.2-2.3 times higher than that of natural teeth. The thickness discrimination was significantly higher than that of natural teeth with an SMD of 1.2368 (95% CI, 0.8699-1.6038) and a P < 0.0001. CONCLUSION: This meta-analysis suggested that both tactile sensibility and thickness discrimination thresholds of implants were significantly higher than those of natural teeth. This meta-analysis reconfirms that sensation differences between dental implants and natural teeth exist.

Mouth breathing reduces oral function in adolescence.

Although humans breathe naturally through the nostrils, mouth breathing in children has recently gathered attention. In this study, we hypothesized that tongue function and its related maxillofacial morphology would affect breathing in adolescence. To verify this hypothesis, we examined the association between breathing patterns, including mouth and nasal breathing; oral functions, including tongue motor function; and craniofacial morphology during adolescence, which has not been investigated till date. C3-H, which indicates the anteroposterior position of the hyoid bone in relation to the third cervical vertebra, was significantly smaller in mouth-breathers than in nasal-breathers. Lip-closing force, tongue pressure, and masticatory efficiency were lower in the order of nasal-breathers, oronasal-breathers, and mouth-breathers, and the values for mouth-breathers were significantly lower than those for nasal-breathers. Tongue pressure alone was identified as a significant independent variable, with an odds ratio of 1.063 (95% confidence interval, 1.006-1.123; p < 0.05). Our results indicate a relationship between mouth breathing and the lip-closing force, tongue pressure, and masticatory efficiency, as well as the significance of tongue pressure on mouth breathing in adolescents. The findings highlight the importance of clarifying the pathophysiology of mouth breathing and its underlying causes.

Effect of denture adhesives on masticatory performance: Multicenter randomized controlled trial.

PURPOSE: The purpose of this study is to investigate the effects of denture adhesives on masticatory performance via a 10-center, parallel, randomized, controlled trial of complete denture wearers in Japan. METHODS: The trial was conducted between September 2013 and October 2016. The inclusion criteria were complete edentulism, willingness to undergo new complete denture treatment, and willingness to return for recall treatment. The exclusion criteria were age 90 years or older, presence of severe systemic illness, inability to understand the questionnaires, wearing metal base complete dentures, denture adhesive user, wearing prosthetics for maxillofacial defects, wearing complete dentures with tissue conditioners, and severe xerostomia. Randomization of the powder-type denture adhesive (powder), cream-type denture adhesive (cream), and control (saline) groups was performed using a sealed envelope system. Masticatory performance was measured using color-changeable chewing gum. Intervention blinding was not feasible. RESULTS: Sixty-seven control, 69 powder, and 64 cream participants are analyzed using the intention-to-treat principle. The participants in all groups show significantly improved masticatory performance at post-intervention (paired t-test with Bonferroni correction P < 0.0001). However, no significant difference in masticatory performance is detected among the three groups (one-way analysis of variance). A significant negative correlation between pre- and post-changes in masticatory performance and intraoral condition scores is observed (Pearson's correlation coefficient, P < 0.0001). CONCLUSIONS: Although denture adhesives improved the masticatory performance of complete denture wearers, their clinical effects are comparable to those of saline solution. The use of denture adhesives is more effective in complete denture wearers with unsatisfactory intraoral conditions.

Robotics in Dentistry: A Narrative Review.

BACKGROUND: Robotics is progressing rapidly. The aim of this study was to provide a comprehensive overview of the basic and applied research status of robotics in dentistry and discusses its development and application prospects in several major professional fields of dentistry. METHODS: A literature search was conducted on databases: MEDLINE, IEEE and Cochrane Library, using MeSH terms: ["robotics" and "dentistry"]. RESULT: Forty-nine articles were eventually selected according to certain inclusion criteria. There were 12 studies on prosthodontics, reaching 24%; 11 studies were on dental implantology, accounting for 23%. Scholars from China published the most articles, followed by Japan and the United States. The number of articles published between 2011 and 2015 was the largest. CONCLUSIONS: With the advancement of science and technology, the applications of robots in dental medicine has promoted the development of intelligent, precise, and minimally invasive dental treatments. Currently, robots are used in basic and applied research in various specialized fields of dentistry. Automatic tooth-crown-preparation robots, tooth-arrangement robots, drilling robots, and orthodontic archwire-bending robots that meet clinical requirements have been developed. We believe that in the near future, robots will change the existing dental treatment model and guide new directions for further development.

Effective use of an extraoral vacuum in preventing the dispersal of particulate matter from metal dental materials.

OBJECTIVES: When dentists adjust prostheses at the dental chairside, particulate matter (PM) from the dental material is dispersed. Little is known about the effective use of an extraoral vacuum (EOV) in preventing PM dispersal. This study aimed to evaluate the effective use of an EOV in preventing the dispersal of metal PM in dental offices. METHODS: The following experimental conditions were planned: the distance from the EOV to the metallic materials (50, 100, 150, and 200 mm), the horizontal angle between the long axis of the micromotor handpiece and EOV (0°, 45°, and 90°), and the operating time of the EOV (during grinding, during grinding and 1 min thereafter, during grinding and the preceding 1 min, 1 min before and after grinding, and during grinding). Carborundum and silicone points were used for grinding and PM dispersal. Diameters (0.3, 0.5, 1.0, and 3.0 µm) were measured using a laser particle counter. RESULTS: Depending on the instrument used to grind, there were undetectable PMs of different diameters (Carborundum point: 0.3 and 0.5 µm, Silicone point: 0.3 µm). PMNs were reduced as the distance from the EOV to metal materials decreased. Operating the EOV before grinding along the long axis of the micromotor handpiece was effective in reducing the PMNs. CONCLUSION: PMNs dispersed when grinding metals were effectively reduced by positioning the EOV closer to the grinding surface (within 150 mm) along the long axis of the micromotor handpiece and operating the EOV before grinding.

2-methacryloyloxyethyl phosphorylcholine polymer treatment prevents Candida albicans biofilm formation on acrylic resin.

PURPOSE: We aimed to evaluate the effectiveness of photoreactive 2-methacryloyloxyethyl phosphorylcholine (MPC) in inhibiting Candida albicans biofilm formation on polymethyl methacrylate (PMMA) and assess its mechanism and need for re-application by evaluating its interaction with salivary mucin and durability during temperature changes. METHODS: PMMA discs were used as specimens. The MPC coating was applied using the spray and cure technique for the treatment groups, whereas no coating was applied to the control. The MPC treatment (MT) groups were further differentiated based on the number of thermal cycles involved (0, 1000, 2500, and 5000). The optical density was measured to assess mucin adsorption (MA). Contact angle (CA) was calculated to evaluate surface hydrophilicity. The presence of MPC components on the PMMA surface was assessed using X-ray photoelectron spectroscopy (XPS). C. albicans biofilms were evaluated qualitatively (scanning electron microscope images) and quantitatively (colony-forming units (CFUs)). Statistical analysis was conducted using two-way analysis of variance and Tukey's multiple comparison test. RESULTS: MA rate and CA increased significantly in the MT groups, which exhibited significantly fewer CFUs and thinner biofilms than those of the control group. Based on the XPS, MA, and CFU evaluations, the durability and efficacy of the MPC coating were considered stable up to 2500 thermal cycles. Additionally, a significant interaction was observed between mucin concentration and MPC efficacy. CONCLUSIONS: The photoreactive MPC coating, which was resistant to temperature changes for approximately 3 months, effectively prevented C. albicans biofilm formation by modifying surface hydrophilicity and increasing mucin adsorption.

Effects of denture adhesives on denture retention and occlusal forces in complete denture wearers: A multicenter, randomized controlled trial.

PURPOSE: This study aimed to determine the effects of denture adhesives on denture retention and occlusal force in complete denture wearers in a multicenter, randomized, parallel-group controlled trial. METHODS: Two hundred edentulous patients wearing complete dentures were allocated to three groups: powder-type denture adhesive, cream-type denture adhesive, and control (saline solution). Denture adhesives and saline solution were applied to the dentures for 4 days. The retentive force of the dentures and occlusal force were measured using a force transducer occlusal force meter at baseline and after 4 days of intervention. In addition to between-group comparisons, subgroup analyses of denture retention and occlusal force were performed based on the level of difficulty of the edentulism treatment. The levels were ranked as I (easy), II, III, and IV (difficult). RESULTS: Cream-type denture adhesives significantly improved the retentive force of the dentures (P<0.01) and occlusal force (P<0.05), with no significant differences between baseline and post-intervention forces in the powder-type denture adhesive and control groups. In within-group comparisons, cream-type denture adhesives improved both the retentive and occlusal forces at Level II (P<0.05), and powder-type denture adhesives improved the occlusal force at Level II (P<0.01). CONCLUSIONS: Application of cream-type denture adhesives effectively improves the denture retention and occlusal force in complete denture wearers with a moderate degree of difficulty during edentulism treatment.

Prosthodontic treatment can improve the ingestible food profile in Japanese adult outpatients.

PURPOSE: To investigate the effect of prosthodontic treatment on the ingestible food profile in adult Japanese outpatients, and to identify the related risk factors that can deteriorate the profile. METHODS: The participants were 277 outpatients who visited university-based specialty clinics in Japan for prosthodontic treatment. The demographic data, number of present teeth assessed via intraoral examination, and oral health-related quality of life assessed by the total Oral Health Impact Profile (OHIP-J54) scores of all participants were recorded before treatment. Ingestible food profile score (IFS) was recorded using a validated food intake questionnaire. Eligible participants who answered the questionnaire before and after treatment were categorized into five groups based on the prosthodontic treatments they received (i.e., crowns, bridges, removable partial dentures, removable complete dentures, and removable complete and partial dentures). RESULTS: Multivariate analysis of covariance revealed a statistically significant main effect of prosthodontic intervention (time course: before and after treatment) on mean IFS (P=0.035, F=4.526), even after adjusting for covariates (age, number of present teeth, and treatment modality). Multiple linear regression analysis revealed that the low number of present teeth (r=0.427, P<0.001) and a high OHIP-J54 total score (r=-0.519, P<0.001) of the patients at the baseline were significantly associated with their baseline IFSs, even after adjusting for confounding variables. CONCLUSIONS: The findings of this multicenter follow-up study indicate the importance of prosthodontic rehabilitation in improving patients' ingestible food profiles.

Stress Reduction Effects during Block-Tapping Task of Jaw in Healthy Participants: Functional Near-Infrared Spectroscopy (fNIRS) Measurements of Prefrontal Cortex Activity.

The purpose of this study was to explore the influence of simple jaw opening and closing task of chewing movements on the activities of the prefrontal cortex (PFC) from the viewpoint of stress reduction. We measured cerebral blood flow (CBF) in the PFC during a block-tapping task of the jaw in healthy participants. Eleven young healthy individuals with normal dentition (7 males and 4 females, mean age 28.0 ± 3.7 years) volunteered for this study. CBF was measured using a wearable, functional near-infrared spectroscopy device. Measurements were taken using the central incisors and first molars at interocclusal distances of 5 and 10 mm. The participants were asked to bite a hard/soft block. CBF in all conditions showed limited variability or decreasing trend compared to resting state before the task. The main effect was observed for interocclusal distance (p = 0.008), and there were no significant differences for measurement area of the PFC, tooth type, and material type. An interaction was found between tooth type and material type. In conclusion, these results suggest that simple and rhythmical chewing motion has an effect of reducing CBF in the PFC and resting the PFC, which is an especially notable aspect of periodontal sensory information in the molar.

Application of artificial intelligence in the dental field: A literature review.

PURPOSE: The purpose of this study was to comprehensively review the literature regarding the application of artificial intelligence (AI) in the dental field, focusing on the evaluation criteria and architecture types. STUDY SELECTION: Electronic databases (PubMed, Cochrane Library, Scopus) were searched. Full-text articles describing the clinical application of AI for the detection, diagnosis, and treatment of lesions and the AI method/architecture were included. RESULTS: The primary search presented 422 studies from 1996 to 2019, and 58 studies were finally selected. Regarding the year of publication, the oldest study, which was reported in 1996, focused on "oral and maxillofacial surgery." Machine-learning architectures were employed in the selected studies, while approximately half of them (29/58) employed neural networks. Regarding the evaluation criteria, eight studies compared the results obtained by AI with the diagnoses formulated by dentists, while several studies compared two or more architectures in terms of performance. The following parameters were employed for evaluating the AI performance: accuracy, sensitivity, specificity, mean absolute error, root mean squared error, and area under the receiver operating characteristic curve. CONCLUSION: Application of AI in the dental field has progressed; however, the criteria for evaluating the efficacy of AI have not been clarified. It is necessary to obtain better quality data for machine learning to achieve the effective diagnosis of lesions and suitable treatment planning.

Semaphorin 3A: A potential target for prevention and treatment of nickel allergy.

Metal allergy is one of the typical immune disorders encountered during the application of dental/medical materials and has a highly complex pathogenic mechanism. Semaphorin 3A (Sema3A), a member of the semaphorin family, is reported to be involved in various immune disorders. However, its role in metal allergy has not been clarified yet. Herein, we show that Sema3A expression was upregulated in nickel (Ni) allergy-induced mouse ear tissue and in NiCl2-stimulated mouse keratinocytes. Moreover, Sema3A regulated tumor necrosis factor-alpha production and mitogen-activated protein kinase activation in keratinocytes. The specific deletion of Sema3A in keratinocytes did not affect immune cell infiltration but reduced edema and ear swelling; it also impeded Th1 responses to cause a slight alleviation in Ni allergy in mice. Our results demonstrate that Sema3A promotes the development of metal allergy and should be explored as a potential target for the prevention and treatment of metal allergy.