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State-of-the-Art Molecular Immunology in Spain
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State-of-the-Art Molecular Immunology in Spain

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 19338

Special Issue Editors

Dr. Yasmina Juarranz

E-Mail Website1 Website2
Guest Editor
Department of Cell Biology, Faculty of Biology and Faculty of Medicine, Complutense University of Madrid (UCM), 28040 Madrid, Spain
Interests: autoimmune diseases; rheumatoid arthritis; immune response; T helper cells; neuropeptides; vasoactive intestinal peptide
Special Issues, Collections and Topics in MDPI journals
Dr. Marina I. Garin

E-Mail Website
Guest Editor
Biomedical Innovation Unit, CIEMAT/CIBERER/IIS Fundación Jiménez Díaz, Madrid, Spain
Interests: development of novel immunotherapy approaches for treating gliomas and brain metastasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A large number of research teams in Spain from different institutions and universities are currently working together to study the molecular mechanisms of immunity, immunogenetics and/or immunopathogenesis. This Special Issue of the International Journal of Molecular Sciences (IJMS) aims to rapidly publish original contributions addressing questions of importance in immunology and related fields in Spain. We welcome manuscripts conveying novel experimental findings that would advance the understanding of molecular mechanisms of immunity, immunogenetics and/or immunopathogenesis. Manuscripts reporting the development or testing of novel therapeutics that target molecular mechanisms are also welcomed.

Dr. Yasmina Juarranz
Dr. Marina Garin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (7 papers)

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Research

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15 pages, 4255 KiB  
Article
Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort
by Sara Salvador-Martín, Paula Zapata-Cobo, Marta Velasco, Laura M. Palomino, Susana Clemente, Oscar Segarra, Cesar Sánchez, Mar Tolín, Ana Moreno-Álvarez, Ana Fernández-Lorenzo, Begoña Pérez-Moneo, Inés Loverdos, Victor Manuel Navas López, Antonio Millán, Lorena Magallares, Ricardo Torres-Peral, Ruth García-Romero, Gemma Pujol-Muncunill, Vicente Merino-Bohorquez, Alejandro Rodríguez, Enrique Salcedo, Beatriz López-Cauce, Ignacio Marín-Jiménez, Luis Menchén, Emilio Laserna-Mendieta, Alfredo J. Lucendo, María Sanjurjo-Sáez and Luis A. López-Fernándezadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2023, 24(2), 1797; https://doi.org/10.3390/ijms24021797 - 16 Jan 2023
Cited by 10 | Viewed by 2587
Abstract
The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. [...] Read more.
The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Spain)
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19 pages, 2124 KiB  
Article
Regulation of Cyclooxygenase-2 Expression in Human T Cells by Glucocorticoid Receptor-Mediated Transrepression of Nuclear Factor of Activated T Cells
by Cristina Cacheiro-Llaguno, Elena Hernández-Subirá, Manuel D. Díaz-Muñoz, Manuel Fresno, Juan M. Serrador and Miguel A. Íñiguez
Int. J. Mol. Sci. 2022, 23(21), 13275; https://doi.org/10.3390/ijms232113275 - 31 Oct 2022
Cited by 4 | Viewed by 1907
Abstract
Cyclooxygenase (COX) is the key enzyme in prostanoid synthesis from arachidonic acid (AA). Two isoforms, named COX-1 and COX-2, are expressed in mammalian tissues. The expression of COX-2 isoform is induced by several stimuli including cytokines and mitogens, and this induction is inhibited [...] Read more.
Cyclooxygenase (COX) is the key enzyme in prostanoid synthesis from arachidonic acid (AA). Two isoforms, named COX-1 and COX-2, are expressed in mammalian tissues. The expression of COX-2 isoform is induced by several stimuli including cytokines and mitogens, and this induction is inhibited by glucocorticoids (GCs). We have previously shown that the transcriptional induction of COX-2 occurs early after T cell receptor (TCR) triggering, suggesting functional implications of this enzyme in T cell activation. Here, we show that dexamethasone (Dex) inhibits nuclear factor of activated T cells (NFAT)-mediated COX-2 transcriptional induction upon T cell activation. This effect is dependent on the presence of the GC receptor (GR), but independent of a functional DNA binding domain, as the activation-deficient GRLS7 mutant was as effective as the wild-type GR in the repression of NFAT-dependent transcription. Dex treatment did not disturb NFAT dephosphorylation, but interfered with activation mediated by the N-terminal transactivation domain (TAD) of NFAT, thus pointing to a negative cross-talk between GR and NFAT at the nuclear level. These results unveil the ability of GCs to interfere with NFAT activation and the induction of pro-inflammatory genes such as COX-2, and explain some of their immunomodulatory properties in activated human T cells. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Spain)
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12 pages, 1806 KiB  
Article
Genetic LGALS1 Variants Are Associated with Heterogeneity in Galectin-1 Serum Levels in Patients with Early Arthritis
by Ana Triguero-Martínez, Emilia Roy-Vallejo, Nuria Montes, Hortensia de la Fuente, Ana María Ortiz, Santos Castañeda, Isidoro González-Álvaro and Amalia Lamana
Int. J. Mol. Sci. 2022, 23(13), 7181; https://doi.org/10.3390/ijms23137181 - 28 Jun 2022
Cited by 3 | Viewed by 1721
Abstract
Galectin 1 (Gal1) exerts immunomodulatory effects leading to therapeutic effects in autoimmune animal models. Patients with rheumatoid arthritis have been reported to show higher Gal1 serum levels than the healthy population. Our study aimed to find genetic variants on the Gal1 gene ( [...] Read more.
Galectin 1 (Gal1) exerts immunomodulatory effects leading to therapeutic effects in autoimmune animal models. Patients with rheumatoid arthritis have been reported to show higher Gal1 serum levels than the healthy population. Our study aimed to find genetic variants on the Gal1 gene (LGALS1) modulating its expression and/or clinical features in patients with early arthritis (EA). LGALS1 was sequenced in 53 EA patients to characterize all genetic variants. Then, we genotyped rs9622682, rs929039, and rs4820293, which covered the main genetic variation in LGALS1, in 532 EA patients. Gal1 and IL-6 serum levels were measured by ELISA and Gal1 also by western blot (WB) in lymphocytes from patients with specific genotypes. Once disease activity improved with treatment, patients with at least one copy of the minor allele in rs9622682 and rs929039 or those with GG genotype in rs4820293 showed significantly higher Gal1 serum levels (p < 0.05). These genotypic combinations were also associated with higher Gal1 expression in lymphocytes by WB and lower IL-6 serum levels in EA patients. In summary, our study suggests that genetic variants studied in LGALS1 can explain heterogeneity in Gal1 serum levels showing that patients with higher Gal1 levels have lower serum IL-6 levels. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Spain)
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10 pages, 1152 KiB  
Article
Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins
by Adriana Ariza, Cristobalina Mayorga, Gádor Bogas, Francesco Gaeta, María Salas, Rocco L. Valluzzi, Marina Labella, Natalia Pérez-Sánchez, Cristiano Caruso, Ana Molina, Tahia D. Fernández, María José Torres and Antonino Romano
Int. J. Mol. Sci. 2022, 23(13), 6992; https://doi.org/10.3390/ijms23136992 - 23 Jun 2022
Cited by 8 | Viewed by 2005
Abstract
Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used [...] Read more.
Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Spain)
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19 pages, 3500 KiB  
Article
Human CD4+CD45RA+ T Cells Behavior after In Vitro Activation: Modulatory Role of Vasoactive Intestinal Peptide
by Raúl Villanueva-Romero, Alicia Cabrera-Martín, Emigdio Álvarez-Corrales, Mar Carrión, Selene Pérez-García, Amalia Lamana, David Castro-Vázquez, Carmen Martínez, Rosa P. Gomariz, Irene Gutiérrez-Cañas and Yasmina Juarranz
Int. J. Mol. Sci. 2022, 23(4), 2346; https://doi.org/10.3390/ijms23042346 - 20 Feb 2022
Cited by 1 | Viewed by 2734
Abstract
Naїve CD4+ T cells, which suffer different polarizing signals during T cell receptor activation, are responsible for an adequate immune response. In this study, we aimed to evaluate the behavior of human CD4+CD45RA+ T cells after in vitro activation [...] Read more.
Naїve CD4+ T cells, which suffer different polarizing signals during T cell receptor activation, are responsible for an adequate immune response. In this study, we aimed to evaluate the behavior of human CD4+CD45RA+ T cells after in vitro activation by anti-CD3/CD28 bead stimulation for 14 days. We also wanted to check the role of the VIP system during this process. The metabolic biomarker Glut1 was increased, pointing to an increase in glucose requirement whereas Hif-1α expression was higher in resting than in activated cells. Expression of Th1 markers increased at the beginning of activation, whereas Th17-associated biomarkers augmented after that, showing a pathogenic Th17 profile with a possible plasticity to Th17/1. Foxp3 mRNA expression augmented from day 4, but no parallel increases were observed in IL-10, IL-2, or TGFβ mRNA expression, meaning that these potential differentiated Treg could not be functional. Both VIP receptors were located on the plasma membrane, and expression of VPAC2 receptor increased significantly with respect to the VPAC1 receptor from day 4 of CD4+CD45RA+ T activation, pointing to a shift in VPAC receptors. VIP decreased IFNγ and IL-23R expression during the activation, suggesting a feasible modulation of Th17/1 plasticity and Th17 stabilization through both VPAC receptors. These novel results show that, without polarizing conditions, CD4+CD45RA+ T cells differentiate mainly to a pathogenic Th17 subset and an unpaired Treg subset after several days of activation. Moreover, they confirm the important immunomodulatory role of VIP, also on naїve Th cells, stressing the importance of this neuropeptide on lymphocyte responses in different pathological or non-pathological situations. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Spain)
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Review

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33 pages, 1394 KiB  
Review
MicroRNAs in T Cell-Immunotherapy
by Sara G. Dosil, Ana Rodríguez-Galán, Francisco Sánchez-Madrid and Lola Fernández-Messina
Int. J. Mol. Sci. 2023, 24(1), 250; https://doi.org/10.3390/ijms24010250 - 23 Dec 2022
Cited by 7 | Viewed by 3646
Abstract
MicroRNAs (miRNAs) act as master regulators of gene expression in homeostasis and disease. Despite the rapidly growing body of evidence on the theranostic potential of restoring miRNA levels in pre-clinical models, the translation into clinics remains limited. Here, we review the current knowledge [...] Read more.
MicroRNAs (miRNAs) act as master regulators of gene expression in homeostasis and disease. Despite the rapidly growing body of evidence on the theranostic potential of restoring miRNA levels in pre-clinical models, the translation into clinics remains limited. Here, we review the current knowledge of miRNAs as T-cell targeting immunotherapeutic tools, and we offer an overview of the recent advances in miRNA delivery strategies, clinical trials and future perspectives in RNA interference technologies. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Spain)
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17 pages, 887 KiB  
Review
IL-1 Family Cytokines in Inflammatory Dermatoses: Pathogenetic Role and Potential Therapeutic Implications
by Helena Iznardo and Luís Puig
Int. J. Mol. Sci. 2022, 23(16), 9479; https://doi.org/10.3390/ijms23169479 - 22 Aug 2022
Cited by 33 | Viewed by 3745
Abstract
The interleukin-1 (IL-1) family is involved in the correct functioning and regulation of the innate immune system, linking innate and adaptative immune responses. This complex family is composed by several cytokines, receptors, and co-receptors, all working in a balanced way to maintain homeostasis. [...] Read more.
The interleukin-1 (IL-1) family is involved in the correct functioning and regulation of the innate immune system, linking innate and adaptative immune responses. This complex family is composed by several cytokines, receptors, and co-receptors, all working in a balanced way to maintain homeostasis. Dysregulation of these processes results in tissue inflammation and is involved in the pathogenesis of common inflammatory dermatoses such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. Therefore, therapeutic targeting of IL-1 pathways has been studied, and several monoclonal antibodies are currently being assessed in clinical trials. So far, promising results have been obtained with anti-IL-36R spesolimab and imsidolimab in pustular psoriasis, and their efficacy is being tested in other conditions. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Immunology in Spain)
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