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Biomolecules
Special Issues
Innate Immunity and Inflammation: From Molecular Mechanisms to Therapeutic Applications
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Innate Immunity and Inflammation: From Molecular Mechanisms to Therapeutic Applications

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 1681

Special Issue Editors

Prof. Dr. Simona Pergolizzi

E-Mail Website
Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, 98166 Messina, Italy
Interests: biology; human anatomy; human immunology; gut inflammation; antioxidant activity; bioactive compounds; immunohistochemistry; confocal fluorescence
Special Issues, Collections and Topics in MDPI journals
Dr. Anthea Miller

E-Mail Website
Guest Editor
San Raffaele University, Rome, Italy
Interests: biology; human anatomy; human immunology; comparative anatomy; gut inflammation; antioxidant activity; bioactive compounds; immunohistochemistry; histology

Special Issue Information

Dear Colleagues,

The innate immune system represents the body’s first line of defense against internal and external threats. Highly conserved throughout evolution, innate immune mechanisms have been extensively studied in organisms ranging from Drosophila melanogaster to humans. Pattern-recognition receptors (PRRs) are key mediators that sense pathogen- and danger-associated molecular patterns, enabling the discrimination of self and non-self and triggering protective immune and inflammatory responses. The initiation, amplification, and resolution of inflammation depend on complex interactions among immune and non-immune cells. While controlled inflammation is crucial for pathogen clearance and tissue homeostasis, dysregulated or chronic inflammation contributes to numerous pathological conditions, including autoimmune and inflammatory diseases.

Recently, advances in molecular and cellular immunology have greatly expanded our understanding of innate immune signaling pathways and their role in health and disease. These discoveries are now being translated into innovative therapeutic approaches that modulate innate immune responses. This Special Issue, titled “Innate Immunity and Inflammation: From Molecular Mechanisms to Therapeutic Applications”, will highlight recent progress in deciphering innate immune pathways and explore how this knowledge can be harnessed for therapeutic benefit. We welcome contributions discussing molecular mechanisms, signaling networks, and novel strategies targeting innate immunity for the treatment of infectious, inflammatory, and autoimmune diseases.

Prof. Dr. Simona Pergolizzi
Dr. Anthea Miller
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 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. Biomolecules 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 2700 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

  • inflammation
  • innate immunity
  • therapeutic targets
  • immune signaling pathways
  • pattern-recognition receptors (PRRs)

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Published Papers (2 papers)

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Review

15 pages, 712 KB  
Review
Intersecting Roles of Estrogens and Neutrophils in Modulating Innate Immunity in Cancer
by Mary Wines-Samuelson, Thomas R. Henson, Raegan J. Myers and Stephen R. Hammes
Biomolecules 2026, 16(5), 617; https://doi.org/10.3390/biom16050617 - 22 Apr 2026
Viewed by 426
Abstract
Steroid-sensitive cancers (e.g., breast, ovarian, uterine, and prostate cancers) are difficult to control and frequently metastasize to lymph nodes, bone, or lung. Although endocrine research has greatly advanced our identification of the direct roles of steroid sex hormones such as androgens and estrogens [...] Read more.
Steroid-sensitive cancers (e.g., breast, ovarian, uterine, and prostate cancers) are difficult to control and frequently metastasize to lymph nodes, bone, or lung. Although endocrine research has greatly advanced our identification of the direct roles of steroid sex hormones such as androgens and estrogens on tumor cells in promoting metastasis or recurrence (e.g., treatment with gonadotropin releasing hormone agonists/antagonists, aromatase inhibitors, and estrogen and androgen receptor antagonists), mechanistic insight regarding indirect effects of steroid hormones, including how the innate immune system responds to cancer and is influenced by steroid hormones, is lacking. Despite technological advances in engineering more robust adaptive immunity to combat tumor growth (e.g., CART or checkpoint inhibitors), there remains a relative lack of investigation into the role of innate immunity as a key defense system. Here we discuss recent studies that highlight the significance of neutrophils and their response to tumorigenic conditions with or without steroid hormones in animal models of cancer. We will describe relationships between steroid hormones and neutrophils, with a specific focus on neutrophil extracellular traps (NETs), and how these interactions modulate tumor growth and invasion. Together, these data indicate that combinatorial regulation of both innate and adaptive immunity in the context of tumorigenesis may improve outcomes in cancer therapies. Full article
(This article belongs to the Special Issue Innate Immunity and Inflammation: From Molecular Mechanisms to Therapeutic Applications)
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Graphical abstract

21 pages, 882 KB  
Review
Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense
by Sarmistha Saha, Luciano Saso and Brigitta Buttari
Biomolecules 2026, 16(3), 360; https://doi.org/10.3390/biom16030360 - 28 Feb 2026
Cited by 1 | Viewed by 966
Abstract
Necroptosis is a regulated form of programmed cell death that helps the body defend itself against infections and cellular stress, especially when apoptosis is blocked. At the center of this process is mixed lineage kinase domain-like (MLKL) protein, the final effector of necroptosis, [...] Read more.
Necroptosis is a regulated form of programmed cell death that helps the body defend itself against infections and cellular stress, especially when apoptosis is blocked. At the center of this process is mixed lineage kinase domain-like (MLKL) protein, the final effector of necroptosis, which is activated downstream of receptor-interacting protein kinase 3 (RIPK3). Once phosphorylated, MLKL changes shape, assembles into oligomers, moves to cellular membranes, and disrupts membrane integrity, ultimately causing cell death. While this RIPK3-MLKL pathway has been well described, it is becoming increasingly clear that MLKL regulation is more complex than originally thought. Recent findings show that MLKL can be modified and activated through alternative mechanisms, even in the absence of RIPK3, and that post-translational modifications such as ubiquitination further fine-tune its activity. Notably, deleting RIPK3 or MLKL does not consistently resolve inflammatory phenotypes in experimental models, suggesting that MLKL has context-dependent functions that extend beyond its role in necroptosis. In line with this idea, MLKL has been implicated in inflammatory signaling, interferon responses, and innate immunity, and is frequently targeted by viruses seeking to evade host defenses. Beyond infections, aberrant MLKL activation contributes to a wide range of chronic diseases, including atherosclerosis, cardiometabolic disorders, liver disease, neurodegeneration, and cancer. In these settings, sustained MLKL-mediated membrane damage and release of danger signals drive ongoing inflammation and tissue injury rather than protective cell elimination. In this review, we provide an overview of MLKL structure, activation, and regulation in both necroptotic and non-necroptotic contexts. We also discuss emerging therapeutic strategies aimed at targeting MLKL activation, membrane engagement, and stability, and highlight key unanswered questions that must be addressed to translate MLKL biology into effective clinical interventions. Full article
(This article belongs to the Special Issue Innate Immunity and Inflammation: From Molecular Mechanisms to Therapeutic Applications)
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