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From Macrophage Biology to Cell and EV-Based Immunotherapies

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 September 2025 | Viewed by 816

Special Issue Editors

Dr. Katarzyna Nazimek

E-Mail Website
Guest Editor
Department of Immunology, The Jagiellonian University College of Medicine, 31-008 Krakow, Poland
Interests: contact and delayed-type hypersensitivity; exosomes; extracellular vesicles; immune regulation via miRNAs; immune tolerance; macrophages; mechanisms underlying hypersensitivity reactions; mouse models of allergy and autoimmunity
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Krzysztof Bryniarski

E-Mail Website
Guest Editor
Department of Immunology, The Jagiellonian University College of Medicine, 31-008 Krakow, Poland
Interests: contact and delayed-type hypersensitivity; exosomes; extracellular vesicles; immune regulation; immune tolerance; mechanisms underlying hypersensitivity reactions; miRNAs; mouse models of allergy and autoimmunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to introduce to you the new Special Issue of the Molecular Immunology Section of the International Journal of Molecular Sciences entitled "From Macrophage Biology to Cell and EV-Based Immunotherapies", which focuses on macrophage-based and macrophage-targeting immunotherapies in cancer, autoimmunity, allergies and other inflammatory conditions.

Increasing knowledge of macrophage heterogeneity has recently led researchers and clinicians to explore their yet unknown roles in cancer, allergic, hypersensitivity and autoimmune reactions. Moreover, uncovering the strategies of regulating/modulating macrophage-mediated processes will greatly facilitate current progress in the development of targeted therapies, including those based on cellular products and extracellular vesicles (EVs).

For over a hundred years, macrophages have received special attention due to their involvement in almost all physiological biological processes. Their disruption leads to pathological inflammatory reactions that dysregulate the functioning of all body systems. Therefore, this Special Issue aims to present the current advances in our understanding of both experimental and clinical aspects of macrophage involvement not only in allergies, hypersensitivities and autoimmunity, but also in inflammation-related conditions, including hypertension and depressive disorder.

We cordially invite all interested researchers to submit their original and review articles covering relevant, basic research and clinical findings so that the Special Issue entitled "From Macrophage Biology to Cell and EV-Based Immunotherapies" can become a platform for sharing experiences between researchers and clinicians.

Please accept our sincerest thanks in advance for participating in this publishing opportunity.

Dr. Katarzyna Nazimek
Prof. Dr. Krzysztof Bryniarski
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.

Keywords

  • macrophage-based
  • macrophage-targeting
  • cancer immunotherapies
  • autoimmunity

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Published Papers (2 papers)

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Research

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22 pages, 3921 KiB  
Article
Quantitative Proteomics Reveals Fh15 as an Antagonist of TLR4 Downregulating the Activation of NF-κB, Inducible Nitric Oxide, Phagosome Signaling Pathways, and Oxidative Stress of LPS-Stimulated Macrophages
by Albersy Armina-Rodriguez, Bianca N. Valdés Fernandez, Carlimar Ocasio-Malavé, Yadira M. Cantres Rosario, Kelvin Carrasquillo Carrión, Loyda M. Meléndez, Abiel Roche Lima, Eduardo L. Tosado Rodriguez and Ana M. Espino
Int. J. Mol. Sci. 2025, 26(14), 6914; https://doi.org/10.3390/ijms26146914 - 18 Jul 2025
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Abstract
There is a present need to develop alternative biotherapeutic drugs to mitigate the exacerbated inflammatory immune responses characteristic of sepsis. The potent endotoxin lipopolysaccharide (LPS), a major component of Gram-negative bacterial outer membrane, activates the immune system via Toll-like receptor 4 (TLR4), triggering [...] Read more.
There is a present need to develop alternative biotherapeutic drugs to mitigate the exacerbated inflammatory immune responses characteristic of sepsis. The potent endotoxin lipopolysaccharide (LPS), a major component of Gram-negative bacterial outer membrane, activates the immune system via Toll-like receptor 4 (TLR4), triggering macrophages and a persistent cascade of inflammatory mediators. Our previous studies have demonstrated that Fh15, a recombinant member of the Fasciola hepatica fatty acid binding protein family, can significantly increase the survival rate by suppressing many inflammatory mediators induced by LPS in a septic shock mouse model. Although Fh15 has been proposed as a TLR4 antagonist, the specific mechanisms underlying its immunomodulatory effect remained unclear. In the present study, we employed a quantitative proteomics approach using tandem mass tag (TMT) followed by LC-MS/MS analysis to identify and quantify differentially expressed proteins that participate in signaling pathways downstream TLR4 of macrophages, which can be dysregulated by Fh15. Data are available via ProteomeXchange with identifier PXD065520. Based on significant fold change (FC) cut-off of 1.5 and p-value ≤ 0.05 criteria, we focused our attention to 114 proteins that were upregulated by LPS and downregulated by Fh15. From these proteins, TNFα, IL-1α, Lck, NOS2, SOD2 and CD36 were selected for validation by Western blot on murine bone marrow-derived macrophages due to their relevant roles in the NF-κB, iNOS, oxidative stress, and phagosome signaling pathways, which are closely associated with sepsis pathogenesis. These results suggest that Fh15 exerts a broad spectrum of action by simultaneously targeting multiple downstream pathways activated by TLR4, thereby modulating various aspects of the inflammatory responses during sepsis. Full article
(This article belongs to the Special Issue From Macrophage Biology to Cell and EV-Based Immunotherapies)
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Review

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47 pages, 1032 KiB  
Review
mTOR Signaling in Macrophages: All Depends on the Context
by Angelika Fedor, Krzysztof Bryniarski and Katarzyna Nazimek
Int. J. Mol. Sci. 2025, 26(15), 7598; https://doi.org/10.3390/ijms26157598 - 6 Aug 2025
Viewed by 190
Abstract
Macrophages are undoubtedly one of the most widely studied cells of the immune system, among other reasons, because they are involved in a wide variety of biological processes. Deregulation of their activity is observed in a number of different disorders, including autoimmune diseases. [...] Read more.
Macrophages are undoubtedly one of the most widely studied cells of the immune system, among other reasons, because they are involved in a wide variety of biological processes. Deregulation of their activity is observed in a number of different disorders, including autoimmune diseases. At the same time, mammalian target of rapamycin (mTOR) is attracting increasing research attention because the pathways dependent on this kinase are activated by a variety of signals, including cytokines and proinflammatory mediators, mediate essential processes for cell survival and metabolism, and can be regulated epigenetically via microRNAs. Therefore, our narrative review aimed to summarize and discuss recent advances in the knowledge of the activation of mTOR signaling in macrophages, with a special focus on autoimmune disorders and the possibility of mTOR control by microRNAs. The summarized research observations allowed us to conclude that the effects of activity and/or inhibition of individual mTOR complexes in macrophages are largely context dependent, and therefore, these broad immunological contexts and other specific conditions should always be taken into account when attempting to modulate these pathways for therapeutic purposes. Full article
(This article belongs to the Special Issue From Macrophage Biology to Cell and EV-Based Immunotherapies)
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