Leveraging Multilayered "Omics" Data for Atopic Dermatitis: A Road Map to Precision Medicine.


:Atopic dermatitis (AD) is a complex multifactorial inflammatory skin disease that affects ~280 million people worldwide. About 85% of AD cases begin in childhood, a significant portion of which can persist into adulthood. Moreover, a typical progression of children with AD to food allergy, asthma or allergic rhinitis has been reported ("allergic march" or "atopic march"). AD comprises highly heterogeneous sub-phenotypes/endotypes resulting from complex interplay between intrinsic and extrinsic factors, such as environmental stimuli, and genetic factors regulating cutaneous functions (impaired barrier function, epidermal lipid, and protease abnormalities), immune functions and the microbiome. Though the roles of high-throughput "omics" integrations in defining endotypes are recognized, current analyses are primarily based on individual omics data and using binary clinical outcomes. Although individual omics analysis, such as genome-wide association studies (GWAS), can effectively map variants correlated with AD, the majority of the heritability and the functional relevance of discovered variants are not explained or known by the identified variants. The limited success of singular approaches underscores the need for holistic and integrated approaches to investigate complex phenotypes using trans-omics data integration strategies. Integrating omics layers (e.g., genome, epigenome, transcriptome, proteome, metabolome, lipidome, exposome, microbiome), which often have complementary and synergistic effects, might provide the opportunity to capture the flow of information underlying AD disease manifestation. Overlapping genes/candidates derived from multiple omics types include FLG, SPINK5, S100A8, and SERPINB3 in AD pathogenesis. Overlapping pathways include macrophage, endothelial cell and fibroblast activation pathways, in addition to well-known Th1/Th2 and NFkB activation pathways. Interestingly, there was more multi-omics overlap at the pathway level than gene level. Further analysis of multi-omics overlap at the tissue level showed that among 30 tissue types from the GTEx database, skin and esophagus were significantly enriched, indicating the biological interconnection between AD and food allergy. The present work explores multi-omics integration and provides new biological insights to better define the biological basis of AD etiology and confirm previously reported AD genes/pathways. In this context, we also discuss opportunities and challenges introduced by "big omics data" and their integration.


Front Immunol


Frontiers in immunology


Ghosh D,Bernstein JA,Khurana Hershey GK,Rothenberg ME,Mersha TB




Has Abstract


2018-12-12 00:00:00








  • The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral Malaria.

    abstract::Cerebral malaria is a life-threatening complication of malaria in humans, and the underlying pathogenic mechanisms are widely analyzed in a murine model of experimental cerebral malaria (ECM). Here, we show abrogation of ECM by hemocoel sporozoite-induced infection of a transgenic Plasmodium berghei line that overexpr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Sato Y,Ries S,Stenzel W,Fillatreau S,Matuschewski K

    更新日期:2019-11-01 00:00:00

  • CD83: Activation Marker for Antigen Presenting Cells and Its Therapeutic Potential.

    abstract::CD83 is a member of the immunoglobulin (Ig) superfamily and is expressed in membrane bound or soluble forms. Membrane CD83 (mCD83) can be detected on a variety of activated immune cells, although it is most highly and stably expressed by mature dendritic cells (DC). mCD83 regulates maturation, activation and homeostas...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Li Z,Ju X,Silveira PA,Abadir E,Hsu WH,Hart DNJ,Clark GJ

    更新日期:2019-06-07 00:00:00

  • Human Tregs Made Antigen Specific by Gene Modification: The Power to Treat Autoimmunity and Antidrug Antibodies with Precision.

    abstract::Human regulatory CD4+ T cells (Tregs) are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. T...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Adair PR,Kim YC,Zhang AH,Yoon J,Scott DW

    更新日期:2017-09-21 00:00:00

  • Cetuximab Reconstitutes Pro-Inflammatory Cytokine Secretions and Tumor-Infiltrating Capabilities of sMICA-Inhibited NK Cells in HNSCC Tumor Spheroids.

    abstract::Immunosuppressive factors, such as soluble major histocompatibility complex class I chain-related peptide A (sMICA) and transforming growth factor beta 1 (TGF-β1), are involved in tumor immune escape mechanisms (TIEMs) exhibited by head and neck squamous cell carcinomas (HNSCCs) and may represent opportunities for the...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Klöss S,Chambron N,Gardlowski T,Weil S,Koch J,Esser R,Pogge von Strandmann E,Morgan MA,Arseniev L,Seitz O,Köhl U

    更新日期:2015-11-02 00:00:00

  • Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects.

    abstract::Delivery of high doses of radiation to thoracic region, particularly with non-small cell lung cancer patients, becomes difficult due to subsequent complications arising in the lungs of the patient. Radiation-induced pneumonitis is an early event evident in most radiation exposed patients observed within 2-4 months of ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Kainthola A,Haritwal T,Tiwari M,Gupta N,Parvez S,Tiwari M,Prakash H,Agrawala PK

    更新日期:2017-05-02 00:00:00

  • Intestinal Dysbiosis in Autoimmune Diabetes Is Correlated With Poor Glycemic Control and Increased Interleukin-6: A Pilot Study.

    abstract::Intestinal dysbiosis associated with immunological deregulation, leaky gut, bacterial translocation, and systemic inflammation has been associated with autoimmune diseases, such as type 1 diabetes (T1D). The aim of this study was to investigate the intestinal dysbiosis in T1D patients and correlate these results with ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Higuchi BS,Rodrigues N,Gonzaga MI,Paiolo JCC,Stefanutto N,Omori WP,Pinheiro DG,Brisotti JL,Matheucci E Jr,Mariano VS,de Oliveira GLV

    更新日期:2018-07-25 00:00:00

  • IL-1 family cytokines trigger sterile inflammatory disease.

    abstract::Inflammation plays vital roles in protective responses against pathogens and tissue repair, however, improper resolution of inflammatory networks is centrally involved in the pathogenesis of many acute and chronic diseases. Extensive advances have been made in recent years to define the inflammatory processes that are...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Lukens JR,Gross JM,Kanneganti TD

    更新日期:2012-10-09 00:00:00

  • Disease Recurrence-The Sword of Damocles in Kidney Transplantation for Primary Focal Segmental Glomerulosclerosis.

    abstract::A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to recurrent FSGS. Clinical and experimental evidence support the h...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Kienzl-Wagner K,Waldegger S,Schneeberger S

    更新日期:2019-07-17 00:00:00

  • Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro.

    abstract::Antibodies are commonly used in organ transplant induction therapy and to treat autoimmune disorders. The effects of some biologics on the human immune system remain incompletely characterized and a deeper understanding of their mechanisms of action may provide useful insights for their clinical application. The goal ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Binder C,Sellberg F,Cvetkovski F,Berglund E,Berglund D

    更新日期:2020-11-11 00:00:00

  • Improved Cytotoxic T Lymphocyte Responses to Vaccination with Porcine Reproductive and Respiratory Syndrome Virus in 4-1BB Transgenic Pigs.

    abstract::Vaccination is the most reliable measure to prevent infectious diseases in domestic animals. Development of novel vaccines demands extensive studies with new technologies, such as using novel adjuvants and immunomodulatory molecules. The co-stimulatory molecule 4-1BB provides a key signal that directs the fate of T ce...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Huang G,Liu X,Duszynski DW,Tang X,El-Ashram S,Liu Z,Suo X,Li Q

    更新日期:2017-12-18 00:00:00

  • Pro-Inflammatory Signaling by IL-10 and IL-22: Bad Habit Stirred Up by Interferons?

    abstract::Interleukin (IL)-10 and IL-22 are key members of the IL-10 cytokine family that share characteristic properties such as defined structural features, usage of IL-10R2 as one receptor chain, and activation of signal transducer and activator of transcription (STAT)-3 as dominant signaling mode. IL-10, formerly known as c...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Mühl H

    更新日期:2013-02-04 00:00:00

  • Induction Phase of Spontaneous Liver Transplant Tolerance.

    abstract::The liver has long been known to possess tolerogenic properties. Early experiments in liver transplantation demonstrated that in animal models, hepatic allografts could be accepted across MHC-mismatch without the use of immunosuppression, and that transplantation of livers from the same donor was capable of inducing t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: McCaughan GW,Bowen DG,Bertolino PJ

    更新日期:2020-09-11 00:00:00

  • Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer's Disease Brain.

    abstract::Abundant clinical, epidemiological, imaging, genetic, molecular, and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer's disease (AD) brain. Despite many years of intense study, the origin and molecular mechan...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Zhao Y,Cong L,Jaber V,Lukiw WJ

    更新日期:2017-09-04 00:00:00

  • Extracellular Vesicles: Packages Sent With Complement.

    abstract::Cells communicate with other cells in their microenvironment by transferring lipids, peptides, RNA, and sugars in extracellular vesicles (EVs), thereby also influencing recipient cell functions. Several studies indicate that these vesicles are involved in a variety of critical cellular processes including immune, meta...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Karasu E,Eisenhardt SU,Harant J,Huber-Lang M

    更新日期:2018-04-11 00:00:00

  • Cytokine-Based Generation of CD49a+Eomes-/+ Natural Killer Cell Subsets.

    abstract::Recent studies have identified CD49a+Eomes- and CD49a+Eomes+ subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a+Eomes-/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Ni X,Fu B,Zhang J,Sun R,Tian Z,Wei H

    更新日期:2018-09-25 00:00:00

  • Immune Evasion Strategies of Trypanosoma brucei within the Mammalian Host: Progression to Pathogenicity.

    abstract::The diseases caused by African trypanosomes (AT) are of both medical and veterinary importance and have adversely influenced the economic development of sub-Saharan Africa. Moreover, so far not a single field applicable vaccine exists, and chemotherapy is the only strategy available to treat the disease. These strictl...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Stijlemans B,Caljon G,Van Den Abbeele J,Van Ginderachter JA,Magez S,De Trez C

    更新日期:2016-06-24 00:00:00

  • SpBark Suppresses Bacterial Infection by Mediating Hemocyte Phagocytosis in an Invertebrate Model, Scylla paramamosain.

    abstract::Scavenger receptors are cell surface membrane-bound receptors that typically bind multiple ligands and promote the removal of endogenous proteins and pathogens. In this study, we characterized a novel scavenger receptor-like protein, namely, SpBark. SpBark was upregulated in hemocytes after challenges with bacteria, s...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Li XC,Zhou J,Zhou JF,Wang Y,Ma H,Wang Y,Zhao S,Fang WH

    更新日期:2019-08-23 00:00:00

  • Corrigendum: l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis.

    abstract::[This corrects the article DOI: 10.3389/fimmu.2017.00839.]. ...

    journal_title:Frontiers in immunology

    pub_type: 已发布勘误


    authors: Mandal A,Das S,Kumar A,Roy S,Verma S,Ghosh AK,Singh R,Abhishek K,Saini S,Sardar AH,Purkait B,Kumar A,Mandal C,Das P

    更新日期:2020-01-31 00:00:00

  • Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies.

    abstract::Health-related quality of life (HRQoL) in common variable immunodeficiency diseases (CVID) was evaluated by different tools, which were mainly used to compare different schedules of immunoglobulins administration in cross-sectional or short-term longitudinal studies. We assessed the HRQoL and psychological status of C...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Tabolli S,Giannantoni P,Pulvirenti F,La Marra F,Granata G,Milito C,Quinti I

    更新日期:2014-11-26 00:00:00

  • Epigenomic Views of Innate Lymphoid Cells.

    abstract::The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Sciumè G,Shih HY,Mikami Y,O'Shea JJ

    更新日期:2017-11-13 00:00:00

  • Alkaline pH Promotes NADPH Oxidase-Independent Neutrophil Extracellular Trap Formation: A Matter of Mitochondrial Reactive Oxygen Species Generation and Citrullination and Cleavage of Histone.

    abstract::pH is highly variable in different tissues and affects many enzymatic reactions in neutrophils. In response to calcium ionophores such as A23187 and ionomycin, neutrophils undergo nicotinamide adenine dinucleotide phosphate oxidase (NOX)-independent neutrophil extracellular trap (NET) formation (NETosis). However, how...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Naffah de Souza C,Breda LCD,Khan MA,de Almeida SR,Câmara NOS,Sweezey N,Palaniyar N

    更新日期:2018-01-09 00:00:00

  • Reverse translation in tuberculosis: neutrophils provide clues for understanding development of active disease.

    abstract::Tuberculosis (TB) is a major health issue globally. Although typically the disease can be cured by chemotherapy in all age groups, and prevented in part in newborn by vaccination, general consensus exists that development of novel intervention measures requires better understanding of disease mechanisms. Human TB is c...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Dorhoi A,Iannaccone M,Maertzdorf J,Nouailles G,Weiner J 3rd,Kaufmann SH

    更新日期:2014-02-05 00:00:00

  • Altered Immune Response and Implantation Failure in Progesterone-Induced Blocking Factor-Deficient Mice.

    abstract::Earlier data suggest that progesterone-induced blocking factor (PIBF) is involved in implantation. The present study therefore aims to investigate the consequences of functional PIBF deficiency during the peri-implantation period. CD1 female mice were injected intraperitoneally with 2 μg anti-PIBF monoclonal antibody ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Csabai T,Pallinger E,Kovacs AF,Miko E,Bognar Z,Szekeres-Bartho J

    更新日期:2020-03-11 00:00:00

  • Differential MicroRNA Expression Levels in Cutaneous Acute Graft-Versus-Host Disease.

    abstract::Allogeneic hematopoietic stem cell transplantation is a curative treatment for numerous hematological malignancies. However, acute graft-versus-host disease (aGvHD) is a major complication affecting 40-70% of all transplant patients, whereby the earliest and most frequent presentation is in the skin. MicroRNAs play a ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Atarod S,Norden J,Bibby LA,Janin A,Ratajczak P,Lendrem C,Pearce KF,Wang XN,O'Reilly S,Van Laar JM,Collin M,Dickinson AM,Crossland RE

    更新日期:2018-07-10 00:00:00

  • FcαRI Dynamics Are Regulated by GSK-3 and PKCζ During Cytokine Mediated Inside-Out Signaling.

    abstract::IgA binding to FcαRI (CD89) is rapidly enhanced by cytokine induced inside-out signaling. Dephosphorylation of serine 263 in the intracellular tail of FcαRI by PP2A and PI3K activation are instrumental in this process. To further investigate these signaling pathways, we targeted downstream kinases of PI3K. Our experim...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Ten Broeke T,Honing H,Brandsma AM,Jacobino S,Bakema JE,Kanters D,van der Linden JAM,Bracke M,Koenderman L,Leusen JHW

    更新日期:2019-01-31 00:00:00

  • Generation of individual diversity: a too neglected fundamental property of adaptive immune system.

    abstract::The fitness gains resulting from development of the adaptive immune system (AIS) during evolution are still the subject of hot debate. A large random repertoire of antigenic receptors is costly to develop and could be the source of autoimmune reactions. And yet, despite their drawbacks, AIS-like systems seem to have b...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Muraille E

    更新日期:2014-05-13 00:00:00

  • Mannan-MOG35-55 Reverses Experimental Autoimmune Encephalomyelitis, Inducing a Peripheral Type 2 Myeloid Response, Reducing CNS Inflammation, and Preserving Axons in Spinal Cord Lesions.

    abstract::CNS autoantigens conjugated to oxidized mannan (OM) induce antigen-specific T cell tolerance and protect mice against autoimmune encephalomyelitis (EAE). To investigate whether OM-peptides treat EAE initiated by human MHC class II molecules, we administered OM-conjugated murine myelin oligodendrocyte glycoprotein pept...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Dagkonaki A,Avloniti M,Evangelidou M,Papazian I,Kanistras I,Tseveleki V,Lampros F,Tselios T,Jensen LT,Möbius W,Ruhwedel T,Androutsou ME,Matsoukas J,Anagnostouli M,Lassmann H,Probert L

    更新日期:2020-11-19 00:00:00

  • Psoriasis: Classical vs. Paradoxical. The Yin-Yang of TNF and Type I Interferon.

    abstract::Chronic plaque psoriasis is a common debilitating skin disease. The identification of the pathogenic role of the TNF/IL-23/TH17 pathway has enabled the development of targeted therapies used in the clinic today. Particularly, TNF inhibitors have become a benchmark for the treatment of numerous chronic inflammatory dis...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Mylonas A,Conrad C

    更新日期:2018-11-28 00:00:00

  • Profile of Histone H3 Lysine 4 Trimethylation and the Effect of Lipopolysaccharide/Immune Complex-Activated Macrophages on Endotoxemia.

    abstract::Macrophage plasticity is a process that allows macrophages to switch between two opposing phenotypes based on differential stimuli. Interferon γ (IFNγ)-primed macrophages stimulated with lipopolysaccharide (LPS) [M(IFNγ+LPS)] produce high levels of pro-inflammatory cytokines such as IL-12, TNFα, and IL-6 and low level...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Ruenjaiman V,Butta P,Leu YW,Pongpanich M,Leelahavanichkul A,Kueanjinda P,Palaga T

    更新日期:2020-01-10 00:00:00

  • Pneumococcal Polysaccharide Vaccine Ameliorates Murine Lupus.

    abstract::Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL-lpr mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Cantarelli C,Guglielmo C,Hartzell S,Salem FE,Andrighetto S,Gazivoda VP,Fiaccadori E,La Manna G,Zaza G,Leventhal J,Tassiulas I,Cravedi P

    更新日期:2019-11-20 00:00:00