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Transgender and gender-diverse (TGD) individuals continue to experience harassment and discrimination across various aspects of life, significantly impacting their physical and mental health. The scarcity of data on their general health, particularly regarding dietary habits, remains a challenge in developing effective healthcare strategies for this population. To address this gap, we analyzed selected dietary habits, physical activity (PA), and body mass index (BMI) among Italian TGD adults compared to the Italian general population (IGP). An online anonymous survey was conducted via the Computer Assisted Web Interviewing technique from June 2020 to June 2021. Participants were enrolled through clinical centers and TGD organizations. Data from 959 TGD adults were analyzed using chi-squared tests and logistic regression models. Key findings indicated that approximately 70% of TGD individuals consumed fewer servings of fruit and vegetables (FV) than recommended (five or more servings per day). Although red meat consumption was lower overall, a greater percentage of TGD individuals reported consuming more than three servings per week. Additionally, 58% of TGD participants indicated that they did not engage in any PA, compared to 36% of the IGP. Notably, significant differences in BMI were identified, with higher rates of overweight and obesity among TGD individuals assigned female at birth. These results underscore the urgent need for tailored nutritional guidelines and inclusive public health strategies to meet the specific health needs of the Italian TGD population. Expanding access to targeted interventions could contribute to improving overall well-being in this marginalized group. [ABSTRACT FROM AUTHOR]

Background: The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIVinduced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line. Methodology/Principal Findings: We used unstimulated or IFN-c-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-c-induced reduction of transepitelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-c-induced apoptosis and up-regulated TNF-a, IL-6 and MIP-3a production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-c did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-c induced arachidonic acid cascade. Conclusion/Significance: Our findings suggest that exogenous Nef, perturbing the IFN-c-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: The gradual aging of population has increased the number of elderly patients receiving kidney transplants. In elderly transplant recipients, careful immunosuppression has to he maintained to avoid both rejection and adverse effects. Clinical protocols after kidney transplantation include use of the calcium channel antagonist diltiazem to ameliorate the hypertensive effect and nephrotoxicity of the immunosuppressant agent ciclosporin (cyclosporine). Objective: Since immune response can he impaired by senescence, we evaluated the influence of diltiazem on lymphocyte proliferation both alone and in the presence of ciclosporin in younger versus older subjects. Methods: Peripheral blood mononuclear cells (PBMC) from younger healthy donors (aged 19-24 years) and older subject; (aged 59-65 years) were Isolated and stimulated with mitogens, recombinant human interleukin-2 (IL-2), purified protein derivative (PPD) antigen from Mycobacterium tuberculosis, and anti-CD3 monoclonal antibody (αCD3 moAh) in the presence or absence of 10-4, 10-5, 10-6. 10-7 mol/L concentrations of diltiazem. In some experiments, lymphocytes from younger and older subjects were used -.-s responder cells in an allogeneic mixed lymphocyte reaction (MLR) in the presence of different concentrations of diltiazem and 10 ng/mL of ciclosporin. Results: We found that PBMC from older subjects were more susceptible lo immunosuppression induced by low concentrations of diltiazem when mitogens were used to stimulate cells. In particular, when pokeweed mitogen was used, diltiazem 10-1 mol/L was associated with statistically significant immunosuppression in older subjects compared with younger subjects. This effect was not observed when IL-2. PPD antigen and αCD3 moAh were used as stimulators. Moreover, in the allogeneic MLR, we found no differences between younger and older subjects when the 10-5, 10-6 and 10-7 mol/l. concentrations of diltiazem were used alone or in the presence of ciclosporin. Only addition of the supratherapeutic 10-4 mol/L concentration of diltiazem to ciclosporin was associated with statistically significant immunosuppression in older versus younger subjects. Discussion: Our results show that PBMC from older subjects are no more susceptible than PBMC from younger subjects to therapeutic doses of diltiazem when T-cell receptors are directly or indirectly involved. On the contrary, when PBMC activation was not mediated by T-cell receptor involvement, as in the case of pokeweed mitogen. susceptibility to a therapeutic concentration of diltiazem in older subjects was enhanced. Moreover, co-administration of therapeutic doses of diltiazem and ciclosporin in an MLR showed no significant differences between younger and older subjects in an in vitro model of lymphocyte response to allogeneic transplantation. Conclusion: Since we found no variations in immunosuppressron between older and younger subjects when therapeutic doses of diltiazem were added to ciclosporin, our data do not discourage the use of diltiazem in older kidney transplant recipients receiving ciclosporin therapy. [ABSTRACT FROM AUTHOR]

Leptin is an adipocyte-derived hormone/cytokine that links nutrition, metabolism, and immune homeostasis and is endowed to modulate several immune responses. We previously demonstrated that both immature and mature human dendritic cells (DCs) express a functional leptin receptor, and we found that leptin activates DCs, licenses them for Th1 priming, and promotes DC survival. Moreover, we found that leptin induces rearrangement of actin microfilaments, leading to uropod and ruffle formation. Here we monitor the effects of leptin on DC migratory capacities, focusing on the intracellular signaling driving cytoskeleton rearrangement. We found that leptin increases immature DC migratory performance both by favoring cytoskeleton dynamics and by up-regulating CCR7 surface expression, thus favoring chemotactic responsiveness. We found that in immature DCs, leptin activates cofilin, favoring the turnover of actin microfilaments, and, by triggering Vav phosphorylation, promotes Rac1 activation. Finally, we found that in immature DCs, leptin up-regulates interleukin-12p70 production on CD40 stimulation and, more importantly, increases their capacity to stimulate activation of autologous CD8+ T cells. Taken altogether, the findings herein highlight the potential use of leptin as an adjuvant tool in vaccination protocols employing ex vivo-generated autologous DCs. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immunity and play a critical role in the first phase of host defense against infection. Interactions between DCs and NK cells have been demonstrated in a variety of settings, with evidence emerging of complex bidirectional crosstalk between the two cell types. The accessory HIV-1 Nef protein is a crucial determinant for viral replication and pathogenesis. We previously demonstrated that Nef, hijacking DC functional activity, subverts the DC arm of immune response to escape the adaptive immune attack. Here, we monitor the effect of Nef on the outcome of the innate immune response, focusing on the impact of Nef on DC/NK crosstalk. We demonstrate that Nef up-regulates the ability of DCs to stimulate the immunoregulatory NK cells (CD56bright) as assessed by the activated phenotype, up-regulation of their proliferative response and INF-γ release. On the other hand, Nef-pulsed DCs inhibit cytotoxic NK cells (CD56dim), as assessed by the reduced HLA-DR surface expression, reduced proliferation and cytotoxic activity. Moreover, in the presence of Nef-pulsed DCs, we found a significant up-regulation of TNF-γ secretion and a Significant reduction of IL-10, GM-CSF, MIP-1α and RANTES secretion. Our findings suggest that the Nef-induced dysregulation in the DC/NK cell crosstalk may represent a potential mechanism through which HIV escapes innate immune surveillance. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) play a crucial role in the generation and regulation of immunity, and their interaction with HIV is relevant in the pathogenesis of AIDS favoring both the initial establishment and spread of the infection and the development of antiviral immunity. HIV-1 Nef is an essential factor for efficient viral replication and pathogenesis, and several studies have been addressed to assess the possible influence of endogenous or exogenous Nef on DC biology. Our findings and other reported data described in this review demonstrate that Nef subverts DC biology interfering with phenotypical, morphological, and functional DC developmental programs, thus representing a viral tool underlying AIDS pathogenesis. This review provides an overview on the mechanism by which Nef, hijacking DC functional activity, may favor both the replication of HIV-I and the escape from immune surveillance. Overall, the findings described here may contribute to the understanding of Nef function, mechanism of action, and cellular partners. Further elucidation of genes induced through Nef signaling in DC could reveal pathways used by DC to drive HIV spread and will be critical to identify therapeutic strategies to bias the DC system toward activation of antiviral immunity instead of facilitating virus dissemination. [ABSTRACT FROM AUTHOR]

Presents a study which investigated whether the HIV-1 Nef protein could be involved in the dysregulation of CD+ T cell responses associated with HIV-1 infection. Brief background on the Nef protein; Methodology; Key findings.

Human immunodeficiency virus (HIV)-1 Nef protein is an essential modulator of AIDS pathogenesis and we have previously demonstrated that rNef enters uninfected human monocytes and induces T cells bystander activation, up-regulating IL-15 production. Since dendritic cells (DCs) play a central role in HIV-1 primary infection we investigated whether rNef affects DCs phenotypic and functional maturation in order to define its role in the immunopathogenesis of AIDS. We found that rNef up-regulates the expression on immature DCs of surface molecules known to be critical for their APC function. These molecules include CD1a, HLA-DR, CD40, CD83, CXCR4, and to a lower extent CD80 and CD86. On the other hand, rNef down-regulates surface expression of HLA-ABC and mannose receptor. The functional consequence of rNef treatment of immature DCs is a decrease in their endocytic and phagocytic activities and an increase in cytokine (IL-1β, IL-12, IL-15, TNF-α) and chemokine (MIP-1α, MIP-1β, IL-8) production as well as in their stimulatory capacity. These results indicate that rNef induces a coordinate series of phenotypic and functional changes promoting DC differentiation and making them more competent APCs. Indeed, Nef induces CD4+ T cell bystander activation by a novel mechanism involving DCs, thus promoting virus dissemination. [Copyright &y& Elsevier]

Leptin is an adipocyte-derived hormone/cytokine that links nutrition, metabolism, and immune homeostasis and is endowed to modulate several immune responses. We previously demonstrated that both immature and mature human dendritic cells (DCs) express a functional leptin receptor, and we found that leptin activates DCs, licenses them for Th1 priming, and promotes DC survival. Moreover, we found that leptin induces rearrangement of actin microfilaments, leading to uropod and ruffle formation. Here we monitor the effects of leptin on DC migratory capacities, focusing on the intracellular signaling driving cytoskeleton rearrangement. We found that leptin increases immature DC migratory performance both by favoring cytoskeleton dynamics and by up-regulating CCR7 surface expression, thus favoring chemotactic responsiveness. We found that in immature DCs, leptin activates cofilin, favoring the turnover of actin microfilaments, and, by triggering Vav phosphorylation, promotes Rac1 activation. Finally, we found that in immature DCs, leptin up-regulates interleukin-12p70 production on CD40 stimulation and, more importantly, increases their capacity to stimulate activation of autologous CD8(+) T cells. Taken altogether, the findings herein highlight the potential use of leptin as an adjuvant tool in vaccination protocols employing ex vivo-generated autologous DCs.