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Roles of Neutrophils in Autoimmune Diseases and Cancers

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: closed (20 March 2026) | Viewed by 627

Special Issue Editor


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Guest Editor
Department of Pediatric Surgery, University Medical Center Mannheim, University Heidelberg, 68167 Mannheim, Germany
Interests: neutrophils; neutrophil extracellular traps; pediatric diseases; pediatric cancers
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Special Issue Information

Dear Colleagues,

Research in the area of autoimmunity and cancers has mainly focused on adaptive immune responses and their broad applications. However, greater attention should be paid to the innate immune response, and especially to neutrophils, which play an invaluable role in host immune defense. Notably, successful neutrophil defense is often associated with inflammatory tissue damage and other disorders such as autoimmune diseases and cancers. This has been linked to the capability of activated neutrophils to release decondensed chromatin decorated with granular proteins known as neutrophil extracellular traps (NETs). NETs act as a scaffold for the aggregation of viable, necrotic and apoptotic cells, as well as crystals and microbes. However, neutrophils have more roles alongside their capability to release NETs, and they are also known as phagocytocic cells, degranulating and producing reactive oxygen species (ROS) among other functions.

Although significant efforts have been made to study neutrophils and NETs in the context of autoimmune diseases and cancer, we still need to broaden our knowledge to develop new and better therapeutical solutions. Therefore, the focus of this Special Issue is to update current research on neutrophils and their various mechanisms of action in autoimmunity and cancer, improving our understanding and enabling the development of new therapeutic strategies. Both review and original articles covering basic, translational or clinical molecular-data-supported research are welcome.

Dr. Jasmin Knopf
Guest Editor

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Keywords

  • neutrophils
  • neutrophil extracellular traps (NETs)
  • autoimmunity
  • autoimmune disease(s)
  • cancer
  • oncology

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Published Papers (1 paper)

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Review

25 pages, 1015 KB  
Review
The Abundance Paradox of S100A8/A9 in Neutrophils: Functional Logic of Calprotectin Dominance in the Cytosolic Proteome
by Kyung-Hee Kim and Byong Chul Yoo
Int. J. Mol. Sci. 2026, 27(9), 3889; https://doi.org/10.3390/ijms27093889 - 27 Apr 2026
Viewed by 95
Abstract
Neutrophils are the most abundant circulating leukocytes and are characterized by a proteome in which granule-associated proteins synthesized during granulopoiesis constitute a major fraction of total cellular protein, reflecting their preloaded effector nature in innate immune defense. A striking feature of neutrophil biology [...] Read more.
Neutrophils are the most abundant circulating leukocytes and are characterized by a proteome in which granule-associated proteins synthesized during granulopoiesis constitute a major fraction of total cellular protein, reflecting their preloaded effector nature in innate immune defense. A striking feature of neutrophil biology is the unusual abundance of the calcium-binding proteins S100A8 and S100A9, which together form the heterodimeric complex known as calprotectin. Early biochemical studies estimated that S100A8/A9 constitutes a substantial fraction of the soluble cytosolic proteome in neutrophils, with later studies often describing it as one of the most abundant protein complexes in these cells. Despite extensive studies on the antimicrobial and inflammatory activities of calprotectin, the biological rationale for this unusual abundance remains incompletely understood. In this review, we examine the structural, biochemical, and regulatory features of S100A8/A9 and explore the potential explanations for its high abundance in the neutrophil cytosol. We first discuss the unique organization of the neutrophil proteome and the transcriptional programs governing granulopoiesis that lead to large-scale production of neutrophil effector proteins. We then review the structural and biochemical properties of S100A8/A9, including its calcium-dependent conformational dynamics and high-affinity transition metal binding, which contribute to antimicrobial defense through nutritional immunity. Several functional hypotheses are considered to explain calprotectin abundance, including roles as an antimicrobial reservoir, a metal-sequestering molecule, a regulator of oxidative stress, and a source of damage-associated molecular patterns. Finally, we discuss the evolutionary logic of neutrophil protein preloading and the implications of calprotectin biology in inflammatory diseases and the tumor microenvironment. Resolving the abundance paradox of S100A8/A9 may reveal fundamental principles governing the organization of innate immune cell proteomes and provide new insights into the strategies used by neutrophils to achieve rapid and effective host defense. Full article
(This article belongs to the Special Issue Roles of Neutrophils in Autoimmune Diseases and Cancers)
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