Hernández Caselles, Trinidad

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Hernández Caselles, Trinidad

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Hernández Caselles, Trinidad

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Universidad de Murcia. Departamento de Bioquímica y Biología Molecular"B" e Inmunología

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Open Access
Cytokine profiles in cord blood in relation to prenatal traffic-related air pollution: The NELA cohort
(Wiley, 2022-02) García-Serna, Azahara M.; Jiménez-Guerrero, Pedro; Cantero-Cano, Esther; Muñoz-García, María; Molina-Ruano, María Dolores; Rojo-Atenza, Encarna; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Ciencias Sociosanitarias
Background: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. Methods: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-β, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. Results: NO2 during the whole pregnancy increased the odds of detection of IL-1β (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. Conclusions: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.
Open Access
Cytokine production by newborns: influence of sex and season of birth
(Natureportfolio, 2022-08-09) García-Serna, Azahara M; Cantero-Cano, Ester; Norte-Muñoz, María; Gil-Buendía, M. Ángeles; Velázquez-Marín, Josefa; Martínez-Torres, Antonia E; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Bioquímica y Biología Molecular B e Inmunología
Background: Immune signatures at birth could be associated with clinical outcomes and will improve our understanding of immunity prenatal programming. Methods: Data come from 235 newborns from the cohort study NELA. Production of cytokines was determined using Luminex technology. Associations between cytokine concentrations with sex and season of birth were examined by multivariate regression models. Results: Umbilical cord blood cells produced high levels of inflammatory cytokines, moderate levels of Th1/Th2/Tr-related cytokines, and low levels of Th17 cytokines. Compared to females, male newborn cells secreted higher levels of Th2 (peptidoglycan-stimulated IL-13, odds ratio [OR] = 2.26; 95% CI 1.18, 4.31, p value = 0.013) and Th17 (polyinosinic:polycytidylic acid-stimulated IL-23, OR = 1.82, 95% CI 1.01, 3.27, p value = 0.046) and lower levels of Th1 (olive-stimulated IL-2, OR = 0.56, 95% CI 0.31, 0.99, p value = 0.047) cytokines. Also, children born during warm seasons showed decreased innate cytokine response to peptidoglycan (IL-6, OR = 0.28, 95% CI 0.15, 0.52, p value < 0.001) compared to those born in cold seasons; meanwhile, adaptive immunity cytokines were more frequently secreted by children born during warm seasons in response to allergen extracts (IL-10, OR = 2.11, 95% CI 1.12, 3.96, p value = 0.020; IL-17F, OR = 3.31, 95% CI 1.83, 5.99, p value < 0.001). Conclusion: Newborns showed specific cytokines signatures influenced by sex and season of birth. Impact: There is a limited number of population-based studies on the immune status at birth and the influence of prenatal and perinatal factors on it. Characterization of cytokine signatures at birth related to the prenatal environment could improve our understanding of immunity prenatal programming. Newborns exhibit specific unstimulated and stimulated cytokine signatures influenced by sex and season of birth. Unstimulated and stimulated cytokine signatures in newborns may be associated with the development of related clinical outcomes later in life.
Open Access
Cytokine profiles in cord blood in relation to prenatal traffic-related air pollution: The NELA cohort
(2022-02-18) García-Serna, Azahara M; Jiménez-Guerrero, Pedro; Cantero-Cano, Esther; Muñoz-García, María; Molina-Ruano, María Dolores; Rojo-Atenza, Encarna; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Bioquímica y Biología Molecular B e Inmunología
Background: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. Methods: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-β, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. Results: NO2 during the whole pregnancy increased the odds of detection of IL-1β (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. Conclusions: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.
Open Access
Prenatal and Perinatal Environmental Influences Shaping the Neonatal Immune System: A Focus on Asthma and Allergy Origins
(MDPI, 2021-04-09) García-Serna, Azahara M; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Bioquímica y Biología Molecular B e Inmunología
It is suggested that programming of the immune system starts before birth and is shaped by environmental influences acting during critical windows of susceptibility for human development. Prenatal and perinatal exposure to physiological, biological, physical, or chemical factors can trigger permanent, irreversible changes to the developing immune system, which may be reflected in cord blood of neonates. The aim of this narrative review is to summarize the evidence on the role of the prenatal and perinatal environment, including season of birth, mode of delivery, exposure to common allergens, a farming environment, pet ownership, and exposure to tobacco smoking and pollutants, in shaping the immune cell populations and cytokines at birth in humans. We also discuss how reported disruptions in the immune system at birth might contribute to the development of asthma and related allergic manifestations later in life.
Restricted
Air pollution from traffic during pregnancy impairs newborn's cord blood immune cells: The NELA cohort
(ELSEVIER, 2021) García-Serna, Azahara M; Jiménez-Guerrero, Pedro; Cantero-Cano, Esther; Muñoz-García, María; Ballesteros-Meseguer, Carmen; Pérez de Los Cobos, Irene; NELA Study group; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Bioquímica y Biología Molecular B e Inmunología
Background: Hazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. Methods: In-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Long-term (whole pregnancy and trimesters) and short-term (15-days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. Results: Mean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 μg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 μg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 μg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. Conclusions: Prenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.
Open Access
The Nutrition in Early Life and Asthma (NELA) birth cohortstudy: Rationale, design, and methods
Alcantara Lopez, Maria V.; Cabezas Herrera, Juan; Jimenez Guerrero, Pedro; Larque Daza, Elvira; Lopez Soler, Concepción; Martinez Gracia, Carmen; Martinez Torres, Antonela; Salvador Garcia, Carmen; Sanchez Solis De Querol, Manuel; Yagüe, Genoveva; Zornoza Moreno, Matilde; Santaella-Pascual, Marina; Diego Puente, Teresa de; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Noguera Velasco, José Antonio; Sola Martínez, Rosa Alba; Mendiola Olivares, Jaime; Morales Bartolomé, Eva; Pérez Fernández, Virginia; Torres Cantero, Alberto Manuel; García-Marcos Álvarez, Luis Vicente; Nieto Díaz, Anibal; Prieto Sánchez, María Teresa; Bioquímica y Biología Molecular B e Inmunología
Open Access
Air pollution from traffic during pregnancy impairs newborn's cord blood immune cells: The NELA cohort
(2020-11-17) García-Serna, Azahara M; Jiménez-Guerrero, Pedro; Cantero-Cano, Esther; Muñoz-García, María; Ballesteros-Meseguer, Carmen; Pérez de los Cobos, Irene; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Morales Bartolomé, Eva; Pérez Fernández, Virginia; García-Marcos Álvarez, Luis Vicente; Bioquímica y Biología Molecular B e Inmunología
Background: Hazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. Methods: In-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Long-term (whole pregnancy and trimesters) and short-term (15-days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. Results: Mean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 μg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 μg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 μg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. Conclusions: Prenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.
Open Access
The Nutrition in Early Life and Asthma (NELA) birth cohort study: Rationale, design, and methods.
(Wiley, 2021-09-19) Cabezas Herrera, Juan; Jiménez Guerrero, Pedro; Larque Daza, Elvira; Martinez Gracia, María del Carmen; Martinez Torres, Antonela; Salvador García, Carme; Sánchez Solís De Querol, Manuel; Yagüe Guirao, Genoveva; Zornoza Moreno, Matilde; López Soler, Concepción; Santaella-Pascual, Marina; Diego Puente, Teresa de; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Sola Martínez, Rosa Alba; Noguera Velasco, José Antonio; Mendiola Olivares, Jaime; Morales Bartolomé, Eva; Pérez Fernández, Virginia; Torres Cantero, Alberto Manuel; García-Marcos Álvarez, Luis Vicente; Nieto Díaz, Anibal; Prieto Sánchez, María Teresa; Bioquímica y Biología Molecular B e Inmunología
Background: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests. Objectives: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility. Population: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19–22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the “Virgen de la Arrixaca” University Clinical Hospital over a 36-month period, from March 2015 to April 2018. Design: Prospective, population-based, maternal-child, birth cohort study. Methods: Questionnaires on exposures and outcome variables were administered to mothers at 20–24 gestation week; 32–36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points. Preliminary results: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months’ visit and 532 children (72%) attending the 18 months’ visit. Conclusion: The NELA cohort will add original and unique knowledge to the developmental origins of asthma.
Open Access
Traffic-related air pollution in utero modifies cytokine responses to stimuli of umbilical cord blood cells: a cohort study
(Elsevier, 2026-01-08) García-Serna, Azahara M.; Martín-Orozco Santiago, María Elena; Jiménez Guerrero, Pedro; Cantero-Cano, Esther; Elena, María del Carmen; Soler-Sánchez, Jesús; Hernández Caselles, Trinidad; García-Marcos Álvarez, Luis Vicente; NELA Study group; Morales Bartolomé, Eva; Física
Objective: To examine the associations between in utero exposure to traffic-related air pollutants (TRAP) and cytokine responses to stimuli in newborns. Methods: Luminex technology was used to assess cytokine responses in umbilical cord blood of 235 newborns of the NELA cohort. Samples were cultured with mitogens, pathogen associated with molecular patterns (PAMPs) stimuli and common environmental allergens. Dispersion/chemical transport modelling was used to estimate in utero residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10) and ozone (O3). Multivariable linear regression models were fitted. Results: Per 10 μg/m3 increase of NO2, IL-6 increased in response to mitogens Concanavalin A (12.5 %, 95 % CI: 3.6, 21.4) and Phytohemagglutinin (PHA) (14.9 %, 95 % CI: 7.3, 22.5); to PAMPs Lipopolysaccharide (LPS) (11.6 %, 95 % CI: 3.8, 19.5), Peptidoglycan (PG) (12.0 %, 95 % CI: 4.1, 20.0) and pI:C (13.0 %, 95 % CI: 4.9, 21.2); and to allergens Der pT (11.6 %, 95 % CI: 3.4, 19.9) and olive extract (9.7 %, 95 % CI: 0.4, 19.0). IL-6 response to PHA also increased in relation to PM (19.0 % per 5 μg/m3 increase in PM2.5, 95 % CI: 5.5, 32.5; and 20.2 % per 10 μg/m3 increase in PM10, 95 % CI: 6.0, 34.4). Per 10 μg/m3 increase of NO2, IFN-α responses to PHA and PG increased by 7.5 % (95 % CI: 0.6, 14.5) and 7.6 % (95 % CI: 0.1, 15.1), respectively. NO2 was also associated with an increased Th1-related IFN-γ response to Concanavalin A (7.5 % per 10 μg/m3 increase, 95 % CI: 0.1, 14.9) and decreased Th2-related IL-5 response to PAMPs PG (􀀀 6.7 %, 95 % CI: 􀀀 12.8, 􀀀 0.7) and pI:C (􀀀 7.6 %, 95 % CI: 􀀀 14.2, 􀀀 0.9). Conclusion: Prenatal exposure to TRAP may promote higher proinflammatory and Th1-related and lower Th2- related cytokine responses to stimuli in the offspring
Open Access
The Nutrition in Early Life and Asthma (NELA) birth cohort study: Rationale, design, and methods
(2022) Alcantara-Lopez, Maria V.; Cabezas-Herrera, Juan; Jimenez-Guerrero, Pedro; Larqué, Elvira; Lopez-Soler, Concepción; Martinez-Gracia, Carmen; Martinez-Torres, Antonela; Salvador-Garcia, Carme; Yagüe-Guirao, Genoveva; Zornoza-Moreno, Matilde; Santaella-Pascual, Marina; Diego Puente, Teresa de; Martín-Orozco Santiago, María Elena; Noguera Velasco, José Antonio; Hernández Caselles, Trinidad; Sola Martínez, Rosa Alba; Mendiola Olivares, Jaime; Morales Bartolomé, Eva; Pérez Fernández, Virginia; Torres Cantero, Alberto Manuel; García-Marcos Álvarez, Luis Vicente; Nieto Díaz, Anibal; Prieto Sánchez, María Teresa; Sánchez-Solís de Querol, Manuel; Ciencias Sociosanitarias
Background: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests. Objectives: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility. Population: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19–22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the “Virgen de la Arrixaca” University Clinical Hospital over a 36-month period, from March 2015 to April 2018. Design: Prospective, population-based, maternal-child, birth cohort study. Methods: Questionnaires on exposures and outcome variables were administered to mothers at 20–24 gestation week; 32–36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points. Preliminary results: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months’ visit and 532 children (72%) attending the 18 months’ visit. Conclusion: The NELA cohort will add original and unique knowledge to the developmental origins of asthma.