Family Functioning in Hispanic Parents of Adolescents: Who Benefits Most from a Family-Based HIV and Substance Use Preventive Intervention?

To understand which families are likely to benefit most from resource-intensive family-based, evidence-based interventions (EBIs), we must examine the key, modifiable determinant of family functioning. The purpose of this study was to (1) identify whether there are subgroups of Hispanic parents that differ meaningfully based on their family functioning at baseline, (2) test whether the Familias Unidas preventive intervention was differentially effective across the baseline family functioning subgroups, and (3) understand the mechanisms of intervention effectiveness within each baseline family functioning subgroup. On a pooled data set of 4 completed efficacy and effectiveness trials of Familias Unidas (n = 1445 low-income, Hispanic immigrant origin, parents and their adolescent between the ages of 12-17), we conducted a series of secondary data analyses. Latent profile analyses revealed four significantly different profiles: (1) low family functioning (n = 210, 14.55%), (2) low-to-moderate family functioning (n = 554, 38.39%), (3) moderate-to-high family functioning (n = 490, 33.96%), and (4) high family functioning (n = 189, 13.10%). A structural equation modeling approach found there were significant differences in intervention effectiveness between the subgroups. The low family functioning subgroup experienced gains in family functioning, and in turn, lower levels of adolescent substance use, internalizing, and externalizing symptoms. The high family functioning subgroup showed significant direct effects of the intervention on adolescent substance use, internalizing, and externalizing symptoms, but no indirect effects through improvements in family functioning. Implications for screening, targeting, and adapting interventions are discussed.

Memory Precursors and Short-Lived Effector T cell Subsets Have Different Sensitivities to TGFß.

After exposure to an antigen, CD8 T cells reach a decision point about their fate: to become either short-lived effector cells (SLECs) or memory progenitor effector cells (MPECs). SLECs are specialized in providing an immediate effector function but have a shorter lifespan and lower proliferative capacity compared to MPECs. Upon encountering the cognate antigen during an infection, CD8 T cells rapidly expand and then contract to a level that is maintained for the memory phase after the peak of the response. Studies have shown that the contraction phase is mediated by TGFß and selectively targets SLECs, while sparing MPECs. The aim of this study is to investigate how the CD8 T cell precursor stage determines TGFß sensitivity. Our results demonstrate that MPECs and SLECs have differential responses to TGFß, with SLECs being more sensitive to TGFß than MPECs. This difference in sensitivity is associated with the levels of TGFßRI and RGS3, and the SLEC-related transcriptional activator T-bet binding to the TGFßRI promoter may provide a molecular basis for increased TGFß sensitivity in SLECs.

Parent Attendance in a Family-Based Preventive Intervention Delivered in Latin America and the United States.

In Latin America, there is an increasing interest in the implementation and dissemination of evidence-based, family-centered interventions to prevent youth behavioral problems. While families' participation in interventions is integral to achieving the interventions' desired impact, little is known about what predicts Latin American families' attendance. The current study provides a unique opportunity to explore the participation of families living in the United States, Ecuador, and Chile in an evidence-based intervention, Familias Unidas. We tested for differences in attendance rates, family functioning variables, and adolescent behavioral problem variables, then applied a hierarchical multiple regression to (a) identify which variables significantly predicted program attendance and (b) assess whether the country in which the intervention was implemented in moderated the relationship between predictors and program attendance. On average, Chilean and Ecuadorian parents were more engaged and attended more sessions than parents living in the United States. Across samples, there was significant differences in family functioning and adolescent behavioral problem variables. However, effective parent-adolescent communication was the only significant predictor of lower program attendance. A significant interaction effect revealed that even though Chilean parents had high parent-adolescent communication, they were more likely to attend sessions, compared to parents living in the United States. We highlight the promise of engaging and retaining families, across U.S. and Latin American samples, into a culturally syntonic, family-based intervention, and discuss potential explanations for success in Chile and Ecuador. Researchers interested in implementing interventions in Latin America could utilize these findings to better target participants and intervention efforts.

A Feasibility Trial of an Online-Only, Family-Centered Preventive Intervention for Hispanics: e-Familias Unidas.

We piloted the preventive intervention e-Familias Unidas, delivered exclusively through the Internet to maximize reach and sustainability. This program is an adaptation of an evidence-based, family-centered intervention that aims to prevent Hispanic adolescent drug use and risky sexual behavior through improving family functioning. The purpose of this feasibility trial was to: (1) explore the use of Facebook and a trusted community champion in the online recruitment of Hispanic parents of adolescents, (2) test an online-only assessment and randomization protocol, (3) pilot intervention delivery via e-familiasunidas.com, and (4) assess pre-post changes in family functioning. We tracked participant recruitment and enrollment via Facebook analytics and REDCap. Intervention completion was tracked via our website. We conducted an ANCOVA to test for between group (e-Familias Unidas vs. control) differences post-intervention. Recruitment lasted for a total of 10 weeks and was divided into three phases, with each phase systematically assessing which strategies maximized recruitment and enrollment. Overall, 93 Hispanic parents enrolled in the study. Of those randomized to the intervention group (n = 46), 70% were engaged and watched an average of 5.4 out of the 12 online videos. We found that participants recruited through a community champion, versus Facebook advertisements, had higher rates of enrollment and intervention completion. There was a significant improvement in parent-adolescent communication for parents who received e-Familias Unidas compared to those in the control group (n = 47). This pilot trial demonstrated it is feasible to recruit, assess, and deliver e-Familias Unidas to Hispanic parents through an online-only platform. Our findings highlight the promise of an online platform to optimize the reach of preventive interventions for underserved populations, to more effectively target participants, and to disseminate sustainable evidence-based interventions. We discuss lessons learned and recommendations for future research.

Socio-Cultural Subgroups of Latina/o Immigrants: A Latent Profile Analysis.

Socio-cultural factors, such as familismo, social support, machismo, and multigroup ethnic identity, are strongly associated with Latina/o immigrants' alcohol misuse and depressive symptoms. However, research has rarely explored whether unobserved groups of Latina/o immigrants with similar socio-cultural factors exist. Latent Profile analysis can illuminate which subgroups to target, or which socio-cultural factors need to be supported, to have an impact on the prevention and treatment of alcohol use and/or depression in the Latina/o immigrant population. Cross sectional data from on ongoing longitudinal investigation was utilized (N= 518 Latina/o adults living in Miami-Dade County, Florida and have immigrated to the US within one year prior to assessment). Latent Profile Analyses (LPA) were conducted utilizing validated measures of familismo, social support, neighborhood collective efficacy, ethnic identity, machismo, caballerismo, and marianismo. The LPA revealed three, significantly different profiles: (1) low socio-cultural protection (n=155, 29.98%), (2) high socio-cultural protection (n=21, 4.06%), and (3) high socio-, low-cultural protection (n=341, 65.96%). Profile membership was associated significantly with immigrant documentation status, education level, and past family history of substance use. Results indicate that Latina/o immigrants in the low socio-cultural protection group had significantly higher alcohol use compared to high socio-, low cultural protection group. No significant differences were found for depressive symptoms. We discuss implications of our findings and encourage researchers to continue to unpack the complexities associated with socio-cultural factors and Latina/o mental and behavioral health. Specifically, research should focus on socio-cultural factors can provide protection from negative health outcomes and increase resiliency among this population.

Enhancing the Routine Screening Infrastructure to Address a Syphilis Epidemic in Miami-Dade County.

BACKGROUND: In a recent sexually transmitted disease surveillance report from the Centers for Disease Control and Prevention, Miami-Dade County had the nation's fourth highest rate of infectious syphilis, with rates of congenital syphilis on the rise. As a public health response, Homestead Hospital, in collaboration with the Florida Department of Health, enhanced their emergency department's routine HIV/HCV "opt-out" screening infrastructure to include a syphilis smart screening algorithm. The purpose of this article is to describe the development, implementation, and evaluation of the algorithm. METHODS: A retrospective evaluation of patient records prompted the development of the algorithm. Homestead Hospital's electronic health record system automatically triggers a syphilis test based on the reason for medical visit (e.g., rash, penile discharge, a positive pregnancy test, historical or present sexually transmitted disease result). If a patient tests positive, he/she is counseled and linked to care. RESULTS: Since implementation (April 2018 to August 2019), the smart screening algorithm triggered 4806 syphilis tests: 122 patients tested positive (2.5% seropositivity). After confirmatory testing, 59 patients were positive for syphilis, of which 27 were pregnant. CONCLUSIONS: The Homestead Hospital and Department of Health-Miami-Dade's response to Miami-Dade County's syphilis problem is innovative and replicable. The program embraces technology, enhances the routine opt-out screening model, and does not affect preexisting workflows. Ultimately, implementation of this algorithm allows patients to get treatment, receive comprehensive prevention services, and, in some cases, avert congenital syphilis.

Characterization of Actinobacillus seminis biofilm formation.

Actinobacillus seminis is an autochthonous gram-negative bacterium that affects reproductive organs, causing epididymitis, low fertility, and occasional abortions in ovine and goats. The virulence factors and the pathogenicity mechanisms of A. seminis have not been clearly elucidated yet. In this work, biofilm production by A. seminis in in vitro assays is described and characterized. After 48-h incubation at 37 °C in trypticase soy broth, A. seminis formed biofilms containing an extracellular matrix comprised mainly of fibrillar material. Microaerophilia or the presence of calcium diminished biofilm formation in approximately 50% and 70%, respectively, but low iron concentrations increased it 40%. Through enzymatic digestion, it was found that proteins were the main component of these biofilms. Structural observations through scanning electron microscopy indicated the presence of a high amount of fibrillar material in which bacteria were immersed. Antibodies against different bacterial surface proteins, such as anti-biofilm matrix and anti-adhesin, diminished biofilm formation in 70% and 25%, respectively; whereas furanone C-30 and LED-209, compounds described as quorum-sensing inhibitors, completely inhibited biofilm formation. In conclusion, environmental conditions can influence strongly biofilm formation in A. seminis, and this could be an advantageous strategy that allows bacteria to persist inside a host.

Evidence-based prevention programs targeting youth mental and behavioral health in primary care: A systematic review.

The objectives of this systematic review were to: 1) identify evidence-based youth (i.e., infancy, pre-school age, school age, and adolescence) mental and behavioral health disorder preventive interventions conducted in or offered by primary care settings, and 2) describe these interventions' characteristics, efficacy, and clinical involvement. Randomized controlled trials that targeted the prevention of mental or behavioral health outcomes for youth and had a connection to primary care were included. The PRISMA guidelines were utilized for two phases: 1) searching PubMed, EMBASE, PsycInfo, CINAHL, and Cochrane databases in January 2017; and 2) searching United States Preventive Services Task Force (USPSTF) Systematic Reviews in November 2017. The two phases revealed 504 and 58 potential articles, respectively. After removal of duplicates, screening of abstracts, and full-text reviews, 19 interventions (infancy: n = 2, pre-school age: n = 3, school age: n = 6, adolescence: n = 8) were included: 1) 10 interventions described in 17 articles from the databases, and 2) 9 interventions described in 11 articles from the USPSTF reviews. The included interventions capitalized on primary care settings as a natural entry point to engage youth and families into interventions without requiring a large amount of clinic involvement. Commonalities of efficacious interventions and recommendations for future research are discussed. The authors encourage primary care providers, mental and behavioral health providers, and/or public health researchers to continue developing and testing preventive interventions, or adapting existing interventions, to be implemented in primary care.

eHealth Familias Unidas: Efficacy Trial of an Evidence-Based Intervention Adapted for Use on the Internet with Hispanic Families.

While substance use and sexual risk behaviors among Hispanic youth continue to be public health concerns, few evidence-based preventive interventions are developed for and implemented with Hispanic/Latino youth. The objective of this study was to evaluate the efficacy of eHealth Familias Unidas, an Internet adaptation of an evidence-based family intervention for Hispanics. A randomized controlled trial design (n = 230) was used to evaluate intervention effects on substance use and condomless sex among a sample of Hispanic eighth graders with behavioral problems. Participants were randomized to eHealth Familias Unidas (n = 113) or prevention as usual (n = 117) and assessed at baseline and 3 and 12 months post baseline. We trained mental health school personnel and community mental health professionals to recruit and deliver the Internet-based intervention with Hispanic families. It was hypothesized that, over time, eHealth Familias Unidas would be more efficacious than prevention as usual in reducing drug use (marijuana, cocaine, inhalants, and other drugs), prescription drug use, cigarette use, alcohol use, and condomless sex and that these changes would be mediated by family functioning. Significant intervention effects were found across time for drug use, prescription drug use, and cigarette use. While eHealth Familias Unidas positively affected family functioning, mediation effects were not found. This study demonstrated that family-based eHealth interventions can be efficacious among Hispanic populations when delivered in community settings.

Natural Extracts Abolished Lipid Accumulation in Cells Harbouring non-favourable PNPLA3 genotype.

Background & aims. G-allele of PNPLA3 (rs738409) favours triglycerides accumulation and steatosis. In this study, we examined the effect of quercetin and natural extracts from mushroom and artichoke on reducing lipid accumulation in hepatic cells. MATERIAL AND METHODS: Huh7.5 cells were exposed to oleic acid (OA) and treated with quercetin and extracts to observe the lipid accumulation, the intracellular-TG concentration and the LD size. Sterol regulatory element binding proteins-1 (SREBP-1), peroxisome proliferator-activated receptor (PPARα-γ) and cholesterol acyltransferase (ACAT) gene expression levels were analysed. RESULTS: Quercetin decreased the intracellular lipids, LD size and the levels of intracellular-TG through the down-regulation of SREBP-1c, PPARγ and ACAT1 increasing PPARα. The natural-extracts suppressed OA-induced lipid accumulation and the intracellular-TG. They down-regulate the hepatic lipogenesis through SREBP-1c, besides the activation of lipolysis through the increasing of PPARα expression. CONCLUSIONS: Quercetin and the aqueous extracts decrease intracellular lipid accumulation by down-regulation of lipogenesis and up-regulation of lipolysis.

Dronedarone, an amiodarone analog with improved anti-Leishmania mexicana efficacy.

Dronedarone and amiodarone are cationic lipophilic benzofurans used to treat cardiac arrhythmias. They also have activity against the parasitic protozoan Trypanosoma cruzi, the causative agent of Chagas' disease. They function by disrupting intracellular Ca2+ homeostasis of the parasite and by inhibiting membrane sterol (ergosterol) biosynthesis. Amiodarone also has activity against Leishmania mexicana, suggesting that dronedarone might likewise be active against this organism. This might be of therapeutic interest, since dronedarone is thought to have fewer side effects in humans than does amiodarone. We show here that dronedarone effectively inhibits the growth of L. mexicana promastigotes in culture and, more importantly, has excellent activity against amastigotes inside infected macrophages (the clinically relevant form) without affecting the host cell, with the 50% inhibitory concentrations against amastigotes being 3 orders of magnitude lower than those obtained previously with T. cruzi amastigotes (0.65 nM versus 0.75 µM). As with amiodarone, dronedarone affects intracellular Ca2+ homeostasis in the parasite, inducing an elevation of intracellular Ca2+ levels. This is achieved by rapidly collapsing the mitochondrial membrane potential and inducing an alkalinization of acidocalcisomes at a rate that is faster than that observed with amiodarone. We also show that dronedarone inhibits parasite oxidosqualene cyclase, a key enzyme in ergosterol biosynthesis known to be vital for survival. Overall, our results suggest the possibility of repurposing dronedarone as a treatment for cutaneous, and perhaps other, leishmaniases.

PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) is associated with a higher prevalence of steatosis compared to the general population. AIM: Our aim was to assess the impact of PNPLA3 rs738409 G-allele on steatosis in HCV patients. MATERIAL AND METHODS: We included 474 HCV patients treated with peginterferon plus ribavirin. PNPLA3 rs738409 was genotyped and patients were classified according to alleles and genotypes. Steatosis was detected in 46.4% (220/474). Fibrosis was assessed by Scheuer score. Gene expression was analyzed in Huh7.5 and Huh7 cells using Real Time-PCR. RESULTS: PNPLA3 allele-G was associated with steatosis [54.1% (126/233) vs. 39% (94/241)] (p = 0.0001). In HCV-1, allele-G was related to steatosis [50.6% (82/162) vs. 32.3% (53/164)] (p = 0.001), but did not in HCV-3 [61.9% (26/42) vs. 62% (31/50)] (p = 0.993). PNPLA3 allele-G was associated with steatosis in patients with IL28B-CT/TT [57.7% (82/142) vs. 37.1% (56/151)] (p = 0.0001), but did not in IL28B-CC [47.8% (43/90) vs. 42% (37/88)] (p = 0.442). Independent variables associated with steatosis were: PNPLA3 G-allele [O.R. 1.84 (CI95%: 1.06-3.21); p = 0.007], age [O.R. 1.04 (CI95%: 1.01-1.07); p = 0.017], HCV-genotype 3 [O.R. 2.46 (CI95%: 1.30-4.65); p = 0.006], HOMA > 4 [O.R. 2.72 (CI95%: 1.27-5.82); p = 0.010]. Since PNPLA3 RNA could not be detected on PBMC from HCV patients, an in vitro analysis was performed. Huh7.5 cells infected with JFH1 had a decreased PNPLA3 gene expression (fold inhibition = 3.2 ± 0.2), while Huh7 cells presented increased PNPLA3 gene expression (fold induction = 1.5 ± 0.2). CONCLUSION: PNPLA3 allele-G modulated the development of steatosis, particularly in patients with HCV-1 and IL28B-CT/TT genotype, but was not associated with SVR. Metabolic but not viral steatosis seems to be PNPLA3 regulated. Gene interaction may result in differential PNPLA3 gene expression levels in HCV infection.

NKG2D receptor signaling shapes T cell thymic education.

The role of natural killer group 2D (NKG2D) in peripheral T cells as a costimulatory receptor is well established. However, its contribution to T cell thymic education and functional imprint is unknown. Here, we report significant changes in development, receptor signaling, transcriptional program, and function in T cells from mice lacking NKG2D signaling. In C57BL/6 (B6) and OT-I mice, we found that NKG2D deficiency results in Vß chain usage changes and stagnation of the double-positive stage in thymic T cell development. We found that the expression of CD5 and CD45 in thymocytes from NKG2D deficient mice were reduced, indicating a direct influence of NKG2D on the strength of T cell receptor (TCR) signaling during the developmental stage of T cells. Depicting the functional consequences of NKG2D, peripheral OT-I NKG2D-deficient cells were unresponsive to ovalbumin peptide stimulation. Paradoxically, while αCD3/CD28 agonist antibodies led to phenotypic T cell activation, their ability to produce cytokines remained severely compromised. We found that OT-I NKG2D-deficient cells activate STAT5 in response to interleukin-15 but were unable to phosphorylate ERK or S6 upon TCR engagement, underpinning a defect in TCR signaling. Finally, we showed that NKG2D is expressed in mouse and human thymic T cells at the double-negative stage, suggesting an evolutionarily conserved function during T cell development. The data presented in this study indicate that NKG2D impacts thymic T cell development at a fundamental level by reducing the TCR threshold and affecting the functional imprint of the thymic progeny. In summary, understanding the impact of NKG2D on thymic T cell development and TCR signaling contributes to our knowledge of immune system regulation, immune dysregulation, and the design of immunotherapies.

Longitudinal findings of a U.S. preventive evidence-based family intervention tested among youth in Ecuador: Familias Unidas.

Interventions that address adolescent conduct problems are essential for decreasing negative risk behaviors and promoting positive protective factors among youth. Although interventions have been developed and tested in the United States, preventive evidence-based interventions (EBIs) are less available in Latin American countries such as Ecuador. Therefore, the purpose of this study was to evaluate the efficacy of an evidence-based, parent-centered intervention, Familias Unidas, in preventing/reducing conduct problems, across time, among youth in Guayaquil, Ecuador. Ecuadorian youth (ages 12 through 14) and their respective primary caregiver were recruited from two public schools and randomized to either Familias Unidas or Community Practice. A series of latent growth models were run to test for differences between Familias Unidas and Community Practice on conduct disorder symptoms across three timepoints covering 6 months. Ecuadorian mental health professionals were trained to deliver the evidence-based intervention. Findings indicate no direct relationship between condition and average change in conduct problems at 6 months post baseline. However, indirect effects favoring Familias Unidas over Community Practice were found through improvements in family functioning. Findings highlight that Familias Unidas was efficacious in an international setting and indicate the viability of successfully delivering preventive EBIs in Ecuador.

In vitro anti-Trypanosoma cruzi activity of dronedarone, a novel amiodarone derivative with an improved safety profile.

Amiodarone, a commonly used antiarrhythmic, is also a potent and selective anti-Trypanosoma cruzi agent. Dronedarone is an amiodarone derivative in which the 2,5-diiodophenyl moiety of the parental drug has been replaced with an unsubstituted phenyl group aiming to eliminate the thyroid toxicity frequently observed with amiodarone treatment. Dronedarone has been approved by the Food and Drug Administration (FDA), and its use as a safe antiarrhythmic has been extensively documented. We show here that dronedarone also has potent anti-T. cruzi activity, against both extracellular epimastigotes and intracellular amastigotes, the clinically relevant form of the parasite. The 50% inhibitory concentrations against both proliferative stages are lower than those previously reported for amiodarone. The mechanism of action of dronedarone resembles that of amiodarone, as it induces a large increase in the intracellular Ca(2+) concentration of the parasite, which results from the release of this ion from intracellular storage sites, including a direct effect of the drug on the mitochondrial electrochemical potential, and through alkalinization of the acidocalcisomes. Our results suggest a possible future repurposed use of dronedarone for the treatment of Chagas' disease.

Resurrection and redescription of Clepsinepallida Verrill, 1872 (Hirudinida, Glossiphoniidae) with a phylogeny of the genus Alboglossiphonia.

Alboglossiphoniapallida (Verrill, 1872) comb. nov. is resurrected and redescribed based on morphological and molecular data from specimens of the type locality (New Haven County, Connecticut, USA) that demonstrate it is distinct from North American Alboglossiphoniaheteroclita, European Alboglossiphoniaheteroclita, and Alboglossiphoniapapillosa. Alboglossiphoniapallida is characterized by having dark chromatophores on the dorsal surface arranged lateral to patrilaterally and medially as a thin line or interrupted thin line along with three pairs of eye spots (with the first pair closest together), six pairs of crop ceca, and a united gonopore. Additional sampling of specimens of the genus Alboglossiphonia is needed to understand its phylogeny especially as many species have not been collected since their description.

Metagenomic analysis of the intestinal microbiome in goats on cactus and Salicornia-based diets.

Background: The Peruvian coast is characterized by its arid and saline soils, the cactus being an alternative for arid soils and Salicornia for saline soils. Therefore, it is necessary to develop nutrition based on the intestinal microbiota in goats. Aim: To identify the intestinal microbiota in goats through a metagenomic analysis. Methods: In this study, goats and kids were randomly selected and fed cacti and Salicornia as potential forage species compared to native grass to study the changes in the microbiota using massive sequencing using the 16S rRNA gene as a marker. Results: The sequencing results showed the taxonomic levels of Bacteroidetes and Firmicutes at the phylum level as the most abundant in creole goats' microbiome, varying from 18% to 36% and 47% to 66%, respectively. At the genus level, variants of the genus Ruminococcaceae stand out, related to cellulose degradation, as the most dominant in all samples, followed by Christensenellaceae, Rikenellaceae, and Prevotellaceae. Also, the genus Akkermansia appeared in greater abundance in kids fed with cactus, being necessary for being related to the intestinal mucosa's health and avoiding the adhesion of pathogens to the intestinal epithelium. Conclusion: These microbiota changes based on diets with high fiber content are necessary to understand the adaptation of this species to favorable dietary changes.

A facile solvent extraction method facilitating surface-enhanced Raman spectroscopic detection of ochratoxin A in wine and wheat.

The capability of a solvent-mediated liquid-liquid extraction (LLE) method to improve the detection of ochratoxin A (OTA) in food matrixes using surface-enhanced Raman spectroscopy (SERS) is described. SERS detection of mycotoxins with nanoparticle aggregation is a simple method but with low reproducibility due to the heterogeneous distribution of the nanoparticle aggregates. We evaluated three different LLE protocols to analyze their performance in combination with SERS. A facile extraction method based on sample acidification and addition of chloroform as a separation solvent showed to not only extract OTA from wine and wheat but also facilitate the uniform distribution of the nanoparticles leading to an improvement of the detection signals and the reproducibility. This method enables rapid and simple analysis of mycotoxin Ochratoxin A in food systems.

Corrigendum: The Role of NKG2D in Vitiligo.

[This corrects the article DOI: 10.3389/fimmu.2021.624131.].

The Role of the NKG2D in Vitiligo.

Vitiligo is an acquired multifactorial disease that affects melanocytes and results in skin depigmentation. In this review, we examine the role of cells stress and self-reactive T cells responses. Given the canonical and non-canonical functions of NKG2D, such as authenticating stressed target and enhance TCR signaling, we examine how melanocyte stress leads to the expression of ligands that are recognized by the activating receptor NKG2D, and how its signaling results in the turning of T cells against self (melanocyte suicide by proxy). We also discuss how this initiation phase is followed by T cell perpetuation, as NKG2D signaling results in self-sustained long-lasting T cells, with improved cytolytic properties.