NKT Cell Stimulation with α-Galactosylceramide Results in a Block of Th17 Differentiation after Intranasal Immunization in Mice

In a previous study we demonstrated that intranasal (i.n.) vaccination promotes a Th17 biased immune response. Here, we show that co-administration of a pegylated derivative of α-galactosylceramide (αGCPEG) with an antigen, even in the presence of Th17-polarizing compounds, results in a strong blocking of Th17 differentiation. Additional studies demonstrated that this phenomenon is specifically dependent on soluble factors, like IL-4 and IFNγ, which are produced by NKT cells. Even NK1.1 negative NKT cells, which by themselves produce IL-17A, are able to block Th17 differentiation. It follows that the use of αGCPEG as adjuvant would enable to tailor Th17 responses, according to the specific clinical needs. This knowledge expands our understanding of the role played by NKT cells in overall control of the cytokine microenvironment, as well as in the overall shaping of adaptive immune responses

Suppression in Pb-Pb Collisions at the LHC.

The production of the ψ(2S) charmonium state was measured with ALICE in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV, in the dimuon decay channel. A significant signal was observed for the first time at LHC energies down to zero transverse momentum, at forward rapidity (2.5<y<4). The measurement of the ratio of the inclusive production cross sections of the ψ(2S) and J/ψ resonances is reported as a function of the centrality of the collisions and of transverse momentum, in the region p_{T}<12  GeV/c. The results are compared with the corresponding measurements in pp collisions, by forming the double ratio [σ^{ψ(2S)}/σ^{J/ψ}]_{Pb-Pb}/[σ^{ψ(2S)}/σ^{J/ψ}]_{pp}. It is found that in Pb-Pb collisions the ψ(2S) is suppressed by a factor of ∼2 with respect to the J/ψ. The ψ(2S) nuclear modification factor R_{AA} was also obtained as a function of both centrality and p_{T}. The results show that the ψ(2S) resonance yield is strongly suppressed in Pb-Pb collisions, by a factor of up to ∼3 with respect to pp. Comparisons of cross section ratios with previous Super Proton Synchrotron findings by the NA50 experiment and of R_{AA} with higher-p_{T} results at LHC energy are also reported. These results and the corresponding comparisons with calculations of transport and statistical models address questions on the presence and properties of charmonium states in the quark-gluon plasma formed in nuclear collisions at the LHC

Presencia de obesidad y su asociación con alimentos fuente de fibra y azúcares simples, desde un enfoque de determinantes sociales, en la ciudad de Córdoba durante los años 2020/2021

Obesity is a chronic, heterogeneous and multifactorial disease. Regarding this last concept, the Social Determinants of Health (SDH) become relevant, which influence the development of obesity, such as material and psychosocial circumstances, behavioral factors (including diet), biological factors, social cohesion and the health system. The aim of the present work was to assess the association between intermediate SDH, mainly diet, and obesity in adults residing in Córdoba city in 2020/2021. &nbsp;A population-based, cross-sectional and analytical study was carried out on adults from Córdoba, who were selected based on a multistage random sampling approach. A total of 919 subjects participated in a validated survey that examines different aspects such as demographic, anthropometric measurements and physical activity, and intake through a food frequency questionnaire. The nutritional status was analyzed according to the presence of obesity (through the Body Mass Index). 95 % confidence intervals were estimated to evaluate the prevalence of the disease and models of logistic regression were built to assess the correlation between obesity and SDH of interest, stratifying by sex. The prevalence of obesity was 21,96% (CI95% 0,1929-0,2481). Foods source of simple sugars (g/day) were positively associated with the presence of obesity (OR:1,0008; CI95%1,00003-1,00159). When stratifying by sex, this correlation was significant only in women (OR:1,0012; CI95%1,0001-1,0023). In relation to the intake of food sources of fiber, an inverse correlation between obesity and the quantified consumption per g/day was found. This correlation was significant only in men (OR:0,9958; CI95%0,9921-0,9994). In addition, the weekly intake of this food group was inversely associated with the presence of obesity (OR: 0,9747; CI95% 0,9574-0,9924), being significant only in men (OR: 0,9474; IC95% 0,9101-0,9861). Furthermore, the socio-economic conditions, physical activity, access to a health care system, the presence of comorbidities and exposure to pollutants at work, were linked to the presence of obesity. Considering the SDH approach, a diet with a low fiber and high simple sugar intake has a negative impact on health, being associated with the presence of obesity.La obesidad es una enfermedad crónica, heterogénea y multifactorial. En este último concepto adquieren relevancia los Determinantes Sociales de la Salud (DSS), los cuales influyen en el desarrollo de la obesidad, como las circunstancias materiales, psicosociales, factores conductuales (entre ellos la alimentación), factores biológicos, cohesión social y el sistema de salud. El objetivo del presente trabajo fue valorar la asociación entre los DSS intermedios, principalmente la alimentación, y la obesidad en adultos que residen en la ciudad de Córdoba en 2020/2021. Estudio de base poblacional, transversal y analítico en adultos de la ciudad de Córdoba seleccionados por muestreo aleatorio multietápico. 919 personas respondieron una encuesta validada que indagó sobre aspectos sociodemográficos, medidas antropométricas y actividad física, e ingesta mediante un cuestionario de frecuencia alimentaria. Se analizó el estado nutricional según presencia de obesidad (mediante el índice de masa corporal). Se estimaron intervalos de confianza al 95% para la prevalencia de enfermedad y se construyeron modelos de regresión logística múltiple para evaluar la asociación entre obesidad y los DSS de interés, estratificando según sexo. La prevalencia de obesidad fue del 21,96% (IC95% 0,1929 - 0,2481). Los alimentos fuente de azúcares simples (g/día) se asociaron positivamente con la presencia de obesidad (OR:1,0008; IC95%1,00003-1,00159). Al estratificar por sexo, esta asociación solo fue significativa en mujeres (OR:1,0012; IC95%1,0001-1,0023). En cuanto a la ingesta de alimentos fuente de fibra, se evidenció una asociación inversa con la presencia de obesidad en el consumo cuantificado en g/día, siendo significativo sólo en hombres (OR:0,9958; IC95%0,9921-0,9994). También se demostró que el consumo en veces/semana de estos alimentos se asoció inversamente con la presencia de obesidad (OR: 0,9747; IC95% 0,9574-0,9924), observándose sólo en varones (OR: 0,9474; IC95% 0,9101-0,9861). El nivel socio económico, la actividad física, tener obra social, la presencia de comorbilidades y exposición a contaminantes en trabajo también mostraron asociación con la obesidad. Considerando el enfoque de DSS, una alimentación con un bajo consumo de fibra y elevado en azúcares simples impacta negativamente en la salud, asociándose a la presencia de obesidad

An immunomodulatory peptide related to frenatin 2 from skin secretions of the Tyrrhenian painted frog Discoglossus sardus (Alytidae)

Norepinephrine-stimulated skin secretions of the Tyrrhenian painted frog Discoglossus sardus Tschudi, 1837 (Alytidae) did not contain any peptide with antimicrobial or hemolytic activity. However, peptidomic analysis of the secretions revealed the presence of an abundant peptide with structural similarity to frenatin 2, previously isolated from the Australian frog Litoria infrafrenata (Hylidae). The primary structure of the peptide, termed frenatin 2D, was established as DLLGTLGNLPLPFI.NH2 by automated Edman degradation and mass spectrometry with electron-transfer dissociation (ETD)-based fragmentation and confirmed by chemical synthesis. The structure of a second frenatin 2-related peptide, termed frenatin 2.1D, that was present in much lower abundance was established as GTLGNLPAPFPG. Frenatin 2D (20 μg/ml) significantly stimulated production of the proinflammatory cytokines TNF-α (P<0.05) and IL-1β (P<0.01) by mouse peritoneal macrophages but the peptide did not potentiate the stimulation produced by lipopolysaccharide (LPS). The peptide increased IL-12 production in both unstimulated (P<0.01) and LPS-stimulated (P<0.05) cells but stimulatory effects on IL-6 production were not significant. The biological role of frenatin 2D is unknown but it is speculated that the peptide acts on skin macrophages to produce a cytokine-mediated stimulation of the adaptive immune system in response to invasion by microorganisms

Improved Detection of Cytokines Produced by Invariant NKT Cells

Abstract Invariant Natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after in vivo activation, allowing for the direct detection of a number of cytokines directly ex vivo. However, for some cytokines this approach is suboptimal. Here, we report technical variations that allow the improved detection of IL-4, IL-10, IL-13 and IL-17A ex vivo. Furthermore, we describe an alternative approach for stimulation of iNKT cells in vitro that allows a significantly improved detection of cytokines produced by iNKT cells. Together, these protocols allow the detection of iNKT cell cytokines ex vivo and in vitro with increased sensitivity

Distinct gene expression patterns correlate with developmental and functional traits of iNKT subsets

Invariant natural killer T (iNKT) cells comprise a subpopulation of innate lymphocytes developing in thymus. A new model proposes subdividing murine iNKT cells into iNKT1, 2 and 17 cells. Here, we use transcriptome analyses of iNKT1, 2 and 17 subsets isolated from BALB/c and C57BL/6 thymi to identify candidate genes that may affect iNKT cell development, migration or function. We show that Fcɛr1γ is involved in generation of iNKT1 cells and that SerpinB1 modulates frequency of iNKT17 cells. Moreover, a considerable proportion of iNKT17 cells express IL-4 and IL-17 simultaneously. The results presented not only validate the usefulness of the iNKT1/2/17-concept but also provide new insights into iNKT cell biology

IL-23 Responsive innate-like T cells in spondyloarthritis: the less frequent they are, the more vital they appear

A key role for the IL-23/IL-17 immune axis in spondyloarthritis (SpA) is supported by cumulative evidence from genetic and translational studies and was recently confirmed in clinical trials. Although initially linked to T helper 17 cells, it is now clear that additional unconventional T cell subpopulations respond towards IL-23, including ROR gamma t(+) CD3(+)CD4(-)CD8(-) T cells, TCR gamma delta 17 cells, KIR3DL2(+)CD4(+) T cells and iNKT17 cells. Although these innate-like T cells are present only at low frequencies and often with a specific tissue distribution, it is proposed that they could play a vital function in the development or progression of SpA-related pathology. In this review, we highlight the emerging knowledge on these specialized IL-23 responsive T cells with regard to their relevance in SpA. Finally, we will discuss these findings in light of novel drugs targeting the IL-23/IL-17 axis, currently being tested in SpA patients

Raising the NKT cell family

Natural killer T cells (NKT cells) are CD1d-restricted, lipid antigen–reactive, immunoregulatory T lymphocytes that can promote cell-mediated immunity to tumors and infectious organisms, including bacteria and viruses, yet paradoxically they can also suppress the cell-mediated immunity associated with autoimmune disease and allograft rejection. Furthermore, in some diseases, such as atherosclerosis and allergy, NKT cell activity can be deleterious to the host. Although the precise means by which these cells carry out such contrasting functions is unclear, recent studies have highlighted the existence of many functionally distinct NKT cell subsets. Because their frequency and number vary widely between individuals, it is important to understand the mechanisms that regulate the development and maintenance of NKT cells and subsets thereof, which is the subject of this review