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The Immune Response in the Time of Omics Research
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The Immune Response in the Time of Omics Research

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (1 July 2021) | Viewed by 20307

Special Issue Editors

Dr. Rachele Antonacci

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Guest Editor
Department of Biology, University of Bari “Aldo Moro”, Bari, Italy
Interests: genetics; immunogenetics; genomics; molecular genetics
Dr. Sara Massari

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Guest Editor
Department of Biological and Environmental Science and Technologies, University of Salento, Lecce, Italy
Interests: genetics; immunogenetics; genomics; molecular genetics
Prof. Salvatrice Ciccarese

E-Mail Website
Guest Editor
Department of Biology, University of Bari “Aldo Moro”, Bari, Italy
Interests: genetics; genomics; immunogenomics; genome evolution; T cell receptors genomic organization

Special Issue Information

Dear Colleagues,

The immune system has evolved to protect organisms from pathogens. A multiplicity of cells and molecules act together in a dynamic and complex network capable of specifically recognizing and eliminating an apparently limitless variety of foreign invaders. The complexity of the defensive system reaches its maximum in the higher vertebrates where the two aspects of immunity, innate and adaptive, are closely connected with the only objective to restore the equilibrium present in the organism before the pathogen enters.
However, the immune network is still an incomplete puzzle, and we have a limited understanding of how components of the innate and adaptive immunity interact and work together.
The rapid emergence of high-throughput omics methodologies has made it possible to capture global changes in the host that are induced by an antigenic stimulus. The analysis and integration of datasets hold the promise of providing a broader and deeper understanding of the complex defensive mechanisms.
In this Special Issue, we invite you to submit either original research or review articles that use genomic and functional approaches to unraveling basic topics that contribute to knowledge of the complex molecular mechanisms of the vertebrate immune response.

Dr. Rachele Antonacci
Dr. Sara Massari
Prof. Salvatrice Ciccarese
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. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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.

Keywords

  • B cell receptor
  • T cell receptor
  • MHC
  • Adaptive immunity
  • Innate immunity
  • Evolution
  • Vertebrates
  • Genomics
  • Transcriptome
  • Proteomics

Published Papers (7 papers)

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Research

19 pages, 3786 KiB  
Article
The Organization of the Pig T-Cell Receptor γ (TRG) Locus Provides Insights into the Evolutionary Patterns of the TRG Genes across Cetartiodactyla
by Giovanna Linguiti, Francesco Giannico, Pietro D’Addabbo, Angela Pala, Anna Caputi Jambrenghi, Salvatrice Ciccarese, Serafina Massari and Rachele Antonacci
Genes 2022, 13(2), 177; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13020177 - 19 Jan 2022
Cited by 1 | Viewed by 1540
Abstract
The domestic pig (Sus scrofa) is a species representative of the Suina, one of the four suborders within Cetartiodactyla. In this paper, we reported our analysis of the pig TRG locus in comparison with the loci of species representative of the [...] Read more.
The domestic pig (Sus scrofa) is a species representative of the Suina, one of the four suborders within Cetartiodactyla. In this paper, we reported our analysis of the pig TRG locus in comparison with the loci of species representative of the Ruminantia, Tylopoda, and Cetacea suborders. The pig TRG genomic structure reiterates the peculiarity of the organization of Cetartiodactyla loci in TRGC “cassettes”, each containing the basic V-J-J-C unit. Eighteen genes arranged in four TRGC cassettes, form the pig TRG locus. All the functional TRG genes were expressed, and the TRGV genes preferentially rearrange with the TRGJ genes within their own cassette, which correlates the diversity of the γ-chain repertoire with the number of cassettes. Among them, the TRGC5, located at the 5′ end of the locus, is the only cassette that retains a marked homology with the corresponding TRGC cassettes of all the analyzed species. The preservation of the TRGC5 cassette for such a long evolutionary time presumes a highly specialized function of its genes, which could be essential for the survival of species. Therefore, the maintenance of this cassette in pigs confirms that it is the most evolutionarily ancient within Cetartiodactyla, and it has undergone a process of duplication to give rise to the other TRGC cassettes in the different artiodactyl species in a lineage-specific manner. Full article
(This article belongs to the Special Issue The Immune Response in the Time of Omics Research)
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19 pages, 7713 KiB  
Article
Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution
by Norwin Kubick, Pavel Klimovich, Patrick Henckell Flournoy, Irmina Bieńkowska, Marzena Łazarczyk, Mariusz Sacharczuk, Suniti Bhaumik, Michel-Edwar Mickael and Rajatava Basu
Genes 2021, 12(6), 813; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12060813 - 26 May 2021
Cited by 20 | Viewed by 3349
Abstract
Understanding the evolution of interleukins and interleukin receptors is essential to control the function of CD4+ T cells in various pathologies. Numerous aspects of CD4+ T cells’ presence are controlled by interleukins including differentiation, proliferation, and plasticity. CD4+ T cells have emerged during [...] Read more.
Understanding the evolution of interleukins and interleukin receptors is essential to control the function of CD4+ T cells in various pathologies. Numerous aspects of CD4+ T cells’ presence are controlled by interleukins including differentiation, proliferation, and plasticity. CD4+ T cells have emerged during the divergence of jawed vertebrates. However, little is known about the evolution of interleukins and their origin. We traced the evolution of interleukins and their receptors from Placozoa to primates. We performed phylogenetic analysis, ancestral reconstruction, HH search, and positive selection analysis. Our results indicated that various interleukins’ emergence predated CD4+ T cells divergence. IL14 was the most ancient interleukin with homologs in fungi. Invertebrates also expressed various interleukins such as IL41 and IL16. Several interleukin receptors also appeared before CD4+ T cells divergence. Interestingly IL17RA and IL17RD, which are known to play a fundamental role in Th17 CD4+ T cells first appeared in mollusks. Furthermore, our investigations showed that there is not any single gene family that could be the parent group of interleukins. We postulate that several groups have diverged from older existing cytokines such as IL4 from TGFβ, IL10 from IFN, and IL28 from BCAM. Interleukin receptors were less divergent than interleukins. We found that IL1R, IL7R might have diverged from a common invertebrate protein that contained TIR domains, conversely, IL2R, IL4R and IL6R might have emerged from a common invertebrate ancestor that possessed a fibronectin domain. IL8R seems to be a GPCR that belongs to the rhodopsin-like family and it has diverged from the Somatostatin group. Interestingly, several interleukins that are known to perform a critical function for CD4+ T cells such as IL6, IL17, and IL1B have gained new functions and evolved under positive selection. Overall evolution of interleukin receptors was not under significant positive selection. Interestingly, eight interleukin families appeared in lampreys, however, only two of them (IL17B, IL17E) evolved under positive selection. This observation indicates that although lampreys have a unique adaptive immune system that lacks CD4+ T cells, they could be utilizing interleukins in homologous mode to that of the vertebrates’ immune system. Overall our study highlights the evolutionary heterogeneity within the interleukins and their receptor superfamilies and thus does not support the theory that interleukins evolved solely in jawed vertebrates to support T cell function. Conversely, some of the members are likely to play conserved functions in the innate immune system. Full article
(This article belongs to the Special Issue The Immune Response in the Time of Omics Research)
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27 pages, 15798 KiB  
Article
The T Cell Receptor (TRB) Locus in Tursiops truncatus: From Sequence to Structure of the Alpha/Beta Heterodimer in the Human/Dolphin Comparison
by Giovanna Linguiti, Sofia Kossida, Ciro Leonardo Pierri, Joumana Jabado-Michaloud, Geraldine Folch, Serafina Massari, Marie-Paule Lefranc, Salvatrice Ciccarese and Rachele Antonacci
Genes 2021, 12(4), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12040571 - 14 Apr 2021
Cited by 4 | Viewed by 2522
Abstract
The bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary, and expression study of T. truncatus T cell receptor beta (TRB) [...] Read more.
The bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary, and expression study of T. truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3′ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged T cell receptor α (TRA) and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi-sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the complementarity-determining region according to IMGT numbering (CDR-IMGT) of the dolphin variable V-alpha and beta domains were identified. According to comparative modelization, the atom pair contact sites analysis between the human MH1 grove (G) domains and the T cell receptor (TR) V domains confirms conservation of the structure of the dolphin TR/pMH. Full article
(This article belongs to the Special Issue The Immune Response in the Time of Omics Research)
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22 pages, 6996 KiB  
Article
The Genomic Organisation of the TRA/TRD Locus Validates the Peculiar Characteristics of Dromedary δ-Chain Expression
by Serafina Massari, Giovanna Linguiti, Francesco Giannico, Pietro D’Addabbo, Salvatrice Ciccarese and Rachele Antonacci
Genes 2021, 12(4), 544; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12040544 - 09 Apr 2021
Cited by 5 | Viewed by 2091
Abstract
The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, [...] Read more.
The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) account for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage of the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR α (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site. Full article
(This article belongs to the Special Issue The Immune Response in the Time of Omics Research)
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18 pages, 4853 KiB  
Article
Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events
by Michel-Edwar Mickael, Norwin Kubick, Pavel Klimovich, Patrick Henckell Flournoy, Irmina Bieńkowska and Mariusz Sacharczuk
Genes 2021, 12(2), 254; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12020254 - 10 Feb 2021
Cited by 16 | Viewed by 2968
Abstract
Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a [...] Read more.
Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a debate whether these two processes constitute one mechanism, or they form two evolutionary distinct migration pathways. We used artificial intelligence, phylogenetic analysis, HH search, ancestor sequence reconstruction to investigate further this intriguing question. We found that the two systems share several ancient components, such as RhoA protein that plays a critical role in controlling actin movement in both mechanisms. However, some of the key components differ between these two transmigration processes. CAV1 genes emerged during Trichoplax adhaerens, and it was only reported in transcellular process. Paracellular process is dependent on PECAM1. PECAM1 emerged from FASL5 during Zebrafish divergence. Lastly, both systems employ late divergent genes such as ICAM1 and VECAM1. Taken together, our results suggest that these two systems constitute two different mechanical sensing mechanisms of immune cell infiltrations of the brain, yet these two systems are connected. We postulate that the mechanical properties of the cellular polarity is the main driving force determining the migration pathway. Our analysis indicates that both systems coevolved with immune cells, evolving to a higher level of complexity in association with the evolution of the immune system. Full article
(This article belongs to the Special Issue The Immune Response in the Time of Omics Research)
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20 pages, 3406 KiB  
Article
Epigenetic Evolution of ACE2 and IL-6 Genes: Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates
by Eric R. Sang, Yun Tian, Laura C. Miller and Yongming Sang
Genes 2021, 12(2), 154; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12020154 - 25 Jan 2021
Cited by 29 | Viewed by 4779
Abstract
The current novel coronavirus disease (COVID-19) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. [...] Read more.
The current novel coronavirus disease (COVID-19) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. These host factors are subjected to epigenetic regulation; therefore, relevant analyses on some key genes underlying COVID-19 pathogenesis were performed to longitudinally decipher their epigenetic correlation to COVID-19 susceptibility. The genes of host angiotensin-converting enzyme 2 (ACE2, as the major virus receptor) and interleukin (IL)-6 (a key immuno-pathological factor triggering cytokine storm) were shown to evince active epigenetic evolution via histone modification and cis/trans-factors interaction across different vertebrate species. Extensive analyses revealed that ACE2 ad IL-6 genes are among a subset of non-canonical interferon-stimulated genes (non-ISGs), which have been designated for their unconventional responses to interferons (IFNs) and inflammatory stimuli through an epigenetic cascade. Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of key cis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 and IL6 gene promoters across representative COVID-19-susceptible species compared to unsusceptible ones. The findings characterize ACE2 and IL-6 genes as non-ISGs that respond differently to inflammatory and IFN signaling from the canonical ISGs. The epigenetic properties ACE2 and IL-6 genes may serve as biomarkers to longitudinally predict COVID-19 susceptibility in vertebrates and partially explain COVID-19 inequality in people of different subgroups. Full article
(This article belongs to the Special Issue The Immune Response in the Time of Omics Research)
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20 pages, 789 KiB  
Article
IMGT® Biocuration and Comparative Analysis of Bos taurus and Ovis aries TRA/TRD Loci
by Perrine Pégorier, Morgane Bertignac, Viviane Nguefack Ngoune, Géraldine Folch, Joumana Jabado-Michaloud, Véronique Giudicelli, Patrice Duroux, Marie-Paule Lefranc and Sofia Kossida
Genes 2021, 12(1), 30; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12010030 - 28 Dec 2020
Cited by 8 | Viewed by 2293
Abstract
The adaptive immune response provides the vertebrate immune system with the ability to recognize and remember specific pathogens to generate immunity, and mount stronger attacks each time the pathogen is encountered. T cell receptors are the antigen receptors of the adaptive immune response [...] Read more.
The adaptive immune response provides the vertebrate immune system with the ability to recognize and remember specific pathogens to generate immunity, and mount stronger attacks each time the pathogen is encountered. T cell receptors are the antigen receptors of the adaptive immune response expressed by T cells, which specifically recognize processed antigens, presented as peptides by the highly polymorphic major histocompatibility (MH) proteins. T cell receptors (TR) are divided into two groups, αβ and γδ, which express distinct TR containing either α and β, or γ and δ chains, respectively. The TRα locus (TRA) and TRδ locus (TRD) of bovine (Bos taurus) and the sheep (Ovis aries) have recently been described and annotated by IMGT® biocurators. The aim of the present study is to present the results of the biocuration and to compare the genes of the TRA/TRD loci among these ruminant species based on the Homo sapiens repertoire. The comparative analysis shows similarities but also differences, including the fact that these two species have a TRA/TRD locus about three times larger than that of humans and therefore have many more genes which may demonstrate duplications and/or deletions during evolution. Full article
(This article belongs to the Special Issue The Immune Response in the Time of Omics Research)
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