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25th Anniversary of IJMS: Updates and Advances in “Molecular Immunology”

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: 20 August 2026 | Viewed by 10671

Special Issue Editor

Prof. Dr. Julia Kzhyshkowska

E-Mail Website
Guest Editor
Institute of Transfusion Medicine and Immunology, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
Interests: transcriptional, epigenetic, and metabolic programming of macrophages and their precoursors—corculating monocytes; tumor immunometabolism; macrophage biomarkers of therapy resistance; new molecular targets for TAM reprogramming in solid tumors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The global environment presents new challenges to the immune system, including exposure to the unusual pathogens and significant lifestyle changes, such as an unhealthy diet, low physical activity and increased chronic stress. Under these conditions, the immune system may be unable to combat both exogenous pathogens and endogenous dangers, including metabolic factors and transformed cells. However, our growing knowledge of the molecular mechanisms and different immune cell types and subpopulations that control both innate and adaptive immunity has led to the development of efficient immunotherapeutic molecular and cellular therapies, such as CAR T cells and immune checkpoint inhibitors, which have been translated into clinical practice. At the same time, the application of these tools and their subsequent failure in a number of clinical trials have exposed new levels of complexity in the molecular interactions that control the interaction of immune cells with other cell types in tissues and in the circulation.

Our Special Issue focuses on the identification of key molecular levels and mechanisms at which targets for the therapeutic immunity manipulation can be identified. These levels and mechanisms include the genetic, epigenetic, signaling, protein network; metabolic pathways; and membrane biogenesis levels. The Issue also identifies the bottlenecks where these levels merge and interact. 

We hereby extend an invitation for the submission of research pertaining to the molecular mechanisms that define healthy and pathological functions of immunity. We welcome submissions that address these mechanisms at the fundamental, translational and clinical levels. Our research is particularly focused on the molecular and cellular mechanisms of immunity in cancer, cardiometabolic and autoimmune disorders, neurodegeneration, regenerative medicine and reproductive biology. While these fields represent a primary area of interest, our research is not limited to these areas.

Prof. Dr. Julia Kzhyshkowska
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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.

Keywords

  • inflammation
  • innate immunity
  • adaptive immunity
  • genetics
  • epigenetics
  • immunometabolism
  • receptors
  • cytokines
  • cell therapy
  • immune checkpoint inhibitors

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Published Papers (5 papers)

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Research

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22 pages, 3159 KB  
Article
Immunomodulatory Effects of Phallus indusiatus Extract on Cytokine Responses in PBMCs: Implications for Feline Infectious Peritonitis
by Chularat Hlaoperm, Wassamon Moyadee, Emwalee Wongsaengnoi, Lueacha Tabtimmai, Amonpun Rattanasrisomporn, Atchara Paemanee, Kiattawee Choowongkomon, Christopher Gerner, Oumaporn Rungsuriyawiboon and Jatuporn Rattanasrisomporn
Int. J. Mol. Sci. 2026, 27(3), 1437; https://doi.org/10.3390/ijms27031437 - 31 Jan 2026
Viewed by 505
Abstract
Feline infectious peritonitis (FIP) is a fatal disease driven by feline coronavirus induced immune dysregulation and excessive inflammatory cytokine production. Immunomodulatory agents capable of rebalancing this response are therefore of increasing interest. Phallus indusiatus (P. indusiatus), an edible mushroom containing diverse [...] Read more.
Feline infectious peritonitis (FIP) is a fatal disease driven by feline coronavirus induced immune dysregulation and excessive inflammatory cytokine production. Immunomodulatory agents capable of rebalancing this response are therefore of increasing interest. Phallus indusiatus (P. indusiatus), an edible mushroom containing diverse bioactive compounds, has previously demonstrated antiviral and anti-inflammatory potential. This study investigated the immunomodulatory effects of P. indusiatus extract on peripheral blood mononuclear cells (PBMCs) from healthy cats and FIP cats and characterized its chemical constituents using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). PBMCs were isolated from whole blood and FIP fluid. Cytotoxicity screening identified 19 µg/mL as a non-toxic concentration for subsequent assays. Cytokine responses (IL-1β, IFN-γ, and IL-10) were evaluated following LPS stimulation in PBMCs from whole blood and under basal conditions in PBMCs from FIP fluid after treatment with P. indusiatus extract and dexamethasone. LC–MS/MS profiling combined with STITCH analysis was used to identify bioactive metabolites and their predicted molecular targets. PBMCs derived from FIP fluid exhibited markedly elevated IL-1β and IFN-γ, indicating strong baseline immune activation. P. indusiatus significantly reduced IL-1β and IFN-γ in PBMCs from FIP fluid and suppressed LPS-induced IL-1β and IL-10 in whole-blood PBMCs, demonstrating immunomodulatory patterns comparable to dexamethasone. LC–MS/MS analysis identified compounds including adenosine, phenylalanine, tyrosine, cystathionine, arginine, and sialic acid, which were linked to inflammatory signaling. Overall, the extract exhibited context-dependent modulation of pro- and anti-inflammatory cytokines, suggesting that P. indusiatus may serve as a promising natural adjunctive candidate for managing immune imbalance in cats with FIP. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in “Molecular Immunology”)
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18 pages, 4937 KB  
Article
An Innovative Immunotoxin Design Against Allergy Based on the IL-33 Cytokine and the Ribotoxin α-Sarcin
by Javier Narbona, Rodrigo Lázaro-Gorines, Adrián Gutiérrez-Carmona, Juan Carlos López-Rodríguez, Mayte Villalba and Javier Lacadena
Int. J. Mol. Sci. 2025, 26(19), 9827; https://doi.org/10.3390/ijms26199827 - 9 Oct 2025
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Abstract
Allergies constitute one of the major health problems worldwide, increasing their prevalence in developed countries. To overcome this multifactorial disease, immunotherapy and the use of immune molecules, such as immunotoxins, have arisen as promising therapeutic tools. We have designed, produced, and characterized a [...] Read more.
Allergies constitute one of the major health problems worldwide, increasing their prevalence in developed countries. To overcome this multifactorial disease, immunotherapy and the use of immune molecules, such as immunotoxins, have arisen as promising therapeutic tools. We have designed, produced, and characterized a new immunotoxin called IL-33αS, encompassing the murine IL-33 (mIL-33) as the target domain and the ribotoxin α-sarcin as the toxic domain. IL-33 is a widely described alarmin that binds to the ST2 receptor of a variety of immune cells, including ILC2s, leading to Th2-derived inflammatory response, as occurs in allergic reactions. Both IL-33αS and mIL-33 were successfully produced in the methylotrophic yeast Pichia pastoris and purified to homogeneity through affinity chromatography for their characterization. Both IL-33αS and mIL-33 were able to specifically bind to ST2+ Raw 264.7 cells, and IL-33αS kept the ribonucleolytic activity of α-sarcin, allowing IL-33αS to exhibit cytotoxic effects against ST2+-targeted cells. In addition, IL-33αS induced significantly less secretion of the Th2-linked cytokine IL-13 in comparison to mIL-33, suggesting steric interference produced by the presence of the α-sarcin. These results assess the potential therapeutic effect of this new immunotoxin against allergies, causing ST2-targeted cytotoxicity while avoiding the Th2 cytokine secretion. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in “Molecular Immunology”)
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Review

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21 pages, 649 KB  
Review
Molecular Mechanisms of Transfusion-Associated Immunomodulation and Its Impact in the Critically Ill
by Angel Augusto Pérez-Calatayud and Klaus Görlinger
Int. J. Mol. Sci. 2026, 27(1), 30; https://doi.org/10.3390/ijms27010030 - 19 Dec 2025
Cited by 2 | Viewed by 2305
Abstract
Allogeneic blood transfusion is frequently performed in critically ill patients, but accumulating evidence demonstrates that it is not a biologically neutral intervention. Transfusion-associated immunomodulation (TRIM) encompasses the immunological effects of transfusion, ranging from immune suppression to proinflammatory activation and cancer recurrence, with potential [...] Read more.
Allogeneic blood transfusion is frequently performed in critically ill patients, but accumulating evidence demonstrates that it is not a biologically neutral intervention. Transfusion-associated immunomodulation (TRIM) encompasses the immunological effects of transfusion, ranging from immune suppression to proinflammatory activation and cancer recurrence, with potential impact on morbidity and mortality in the intensive care unit. We conducted a narrative review of recent experimental and clinical evidence on TRIM to describe the molecular pathways involved. We reviewed, randomized trials, metaanalyses, and large observational cohorts to evaluate the clinical relevance of TRIM in critically ill populations. TRIM arises from multiple converging mechanisms. These pathways alter innate and adaptive immunity, leading to increased risk of healthcare-associated infections, transfusion-related acute lung injury, acute kidney injury, multiorgan dysfunction, prolonged length of stay, and cancer recurrence in surgical patients. Blood-sparing strategies, including patient blood management (PBM), mitigate exposure. The impact of storage duration and novel processing technologies remains unclear. There is still a gap in research that needs to be addressed. Transfusion-associated immunomodulation (TRIM) is a phenomenon in which donor leukocytes, extracellular vesicles, microparticles, bioactive lipids, and cytokines interact with the host immune system to produce a spectrum of immunological effects. In critically ill patients, the immune system is already fragile, and these mechanisms predispose patients to infections, pulmonary complications, organ dysfunction, prolonged recovery, and even cancer recurrence. Although TRIM cannot currently be diagnosed through a single biomarker or clinical test, its existence is strongly supported by mechanistic studies and consistent clinical associations between transfusion exposure and adverse outcomes. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in “Molecular Immunology”)
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53 pages, 1390 KB  
Review
Non-Coding RNA in Type 2 Diabetes Cardio–Renal Complications and SGLT2 Inhibitor Response
by Elena Rykova, Elena Shmakova, Igor Damarov, Tatiana Merkulova and Julia Kzhyshkowska
Int. J. Mol. Sci. 2025, 26(22), 11198; https://doi.org/10.3390/ijms262211198 - 19 Nov 2025
Cited by 1 | Viewed by 1851
Abstract
Type 2 diabetes mellitus (T2DM) is characterized by an uncontrolled increase in blood glucose levels and insulin resistance in cells of various tissues. Vascular complications in T2DM have an inflammatory nature. Drugs with different mechanisms of action have been developed and used to [...] Read more.
Type 2 diabetes mellitus (T2DM) is characterized by an uncontrolled increase in blood glucose levels and insulin resistance in cells of various tissues. Vascular complications in T2DM have an inflammatory nature. Drugs with different mechanisms of action have been developed and used to treat T2DM, initially aimed at controlling blood glucose levels. Among them, sodium-glucose cotransporter 2 inhibitors (SGLT2-i) were developed as specific inhibitors of glucose reabsorption in the kidneys, but along with lowering blood glucose levels, they demonstrated multiple (including non-glycemic) positive effects in the treatment of T2DM related to their beneficial effects on the immune system. SGLT2 inhibitors can reduce the risk of diabetic cardiomyopathy (DCM) and chronic kidney disease (CKD) development in patients with and without diabetes. SGLT2-is improve cardio-renal complications through a number of signaling pathways, including those dependent on the involvement of non-coding RNAs (ncRNAs) and their targets. The best-studied classes of ncRNAs are microRNAs, which are short (less than 200 bases) RNAs (miRNAs), long non-coding RNAs (lncRNAs) (more than 200 bases), and circular RNAs (circRNAs). The regulatory effect of ncRNAs has broad physiological significance, and changes in the ncRNAs’ expression are associated with the pathogenesis of different diseases, including T2DM. RNA-seq allows the construction of networks of interactions of lncRNA/circRNA-miRNA-mRNA called competitive endogenous RNA (ceRNA) networks, to identify clinically significant molecular markers, to improve the mechanistic understanding of pathogenesis, and to contribute to the development of new diagnostics and therapies. Our review summarizes the role of non-coding RNA in the action of SGLT2 inhibitors in cardio-renal complications in T2DM. We focus on methods of detection, genetics, and the effects of non-coding RNA. Specific attention is given to the role of non-coding RNAs in the inflammatory reactions of innate immune cells in relation to the SGLT2 inhibitors. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in “Molecular Immunology”)
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15 pages, 1079 KB  
Review
P2Y2 Receptor Signaling in Health and Disease
by Fatemeh Salarpour and Jean Sévigny
Int. J. Mol. Sci. 2025, 26(19), 9815; https://doi.org/10.3390/ijms26199815 - 9 Oct 2025
Cited by 3 | Viewed by 2024
Abstract
P2Y2 receptors are a subclass of G protein-coupled receptors activated by the extracellular nucleotides ATP and UTP. These receptors are widely expressed in multiple tissues—including the brain, lungs, heart, and kidneys—and play pivotal roles in inflammation, wound healing, and cell migration. Through [...] Read more.
P2Y2 receptors are a subclass of G protein-coupled receptors activated by the extracellular nucleotides ATP and UTP. These receptors are widely expressed in multiple tissues—including the brain, lungs, heart, and kidneys—and play pivotal roles in inflammation, wound healing, and cell migration. Through coupling with various G proteins, P2Y2 receptors initiate diverse intracellular signaling pathways that mediate calcium mobilization, cytokine release, and cytoskeletal reorganization. Recent studies highlight their dual roles in health and disease. In physiological contexts, P2Y2 receptors contribute to immune modulation and tissue repair. In pathological conditions, they are implicated in Alzheimer’s disease by promoting non-amyloidogenic processing of amyloid precursor protein and in dry eye disease by enhancing mucin secretion while modulating ocular inflammation. They also influence chloride secretion and mucosal hydration in cystic fibrosis and contribute to inflammatory regulation and epithelial repair in inflammatory bowel disease. Additionally, P2Y2 receptors modulate breast cancer progression by regulating cell adhesion, migration, and matrix remodeling. Their involvement in blood pressure regulation via epithelial sodium channel modulation and their facilitative role in HIV-1 entry further underscore their clinical significance. These multifaceted functions position P2Y2 receptors as promising therapeutic targets for diverse diseases, warranting further investigation for translational applications. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in “Molecular Immunology”)
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