International Journal of Molecular Sciences

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Dear Colleagues,

Various types of cell death, such as apoptosis, pyroptosis, and necrosis, occur in injured tissues. Dead cells subsequently release danger-associated molecule patterns (DAMPs) including DNA, RNA, ATP, uric acid, high-mobility group box 1 (HMGB1), and S100 proteins. These molecules can collectively regulate the migration and activation of various types of immune cells, including granulocytes, lymphocytes, and dendritic cells. The immune cells can produce various cytokines, chemokines, and lipid mediators, thereby modulating the host response to tissue injury and promoting subsequent tissue repair. Thus, innate and acquired immunity is presumed to contribute crucially to the tissue repair process. However, it remains elusive how DAMPs and other mediators coordinate innate and acquired immune responses to tissue injury. Hence, in this Special Issue on tissue injury, we will discuss various types of mediators including DAMPs, cytokines, chemokines, and lipid mediators, which are deeply involved in the innate and acquired immune responses to tissue injuries—particularly those in clinically relevant situations.

Prof. Dr. Naofumi Mukaida
Guest Editor

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Keywords

apoptosis
chemokine
cytokine
danger-associated molecular pattern (DAMP)
dendritic cell
granulocyte
lipid mediator
lymphocyte
necrosis
pyroptosis

Published Papers (2 papers)

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Research

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9 pages, 11160 KiB

Open AccessArticle

Calcium Pyrophosphate Dihydrate Crystals Increase the Granulocyte/Monocyte Progenitor (GMP) and Enhance Granulocyte and Monocyte Differentiation In Vivo

by Nobuyuki Onai and Chie Ogasawara

Int. J. Mol. Sci. 2021, 22(1), 262; https://doi.org/10.3390/ijms22010262 - 29 Dec 2020

Cited by 2 | Viewed by 2481

Abstract

Calcium pyrophosphate dihydrate (CPPD) crystals are formed locally within the joints, leading to pseudogout. Although the mobilization of local granulocytes can be observed in joints where pseudogout has manifested, the mechanism of this activity remains poorly understood. In this study, CPPD crystals were administered to mice, and the dynamics of splenic and peripheral blood myeloid cells were analyzed. As a result, levels of both granulocytes and monocytes were found to increase following CPPD crystal administration in a concentration-dependent manner, with a concomitant decrease in lymphocytes in the peripheral blood. In contrast, the levels of other cells, such as dendritic cell subsets, T-cells, and B-cells, remained unchanged in the spleen, following CPPD crystal administration. Furthermore, an increase in granulocytes/monocyte progenitors (GMPs) and a decrease in megakaryocyte/erythrocyte progenitors (MEPs) were also observed in the bone marrow. In addition, CPPD administration induced production of IL-1β, which acts on hematopoietic stem cells and hematopoietic progenitors and promotes myeloid cell differentiation and expansion. These results suggest that CPPD crystals act as a “danger signal” to induce IL-1β production, resulting in changes in course of hematopoietic progenitor cell differentiation and in increased granulocyte/monocyte levels, and contributing to the development of gout. Full article

(This article belongs to the Special Issue Molecular Mechanism of Innate and Acquired Immunity in Tissue Injury)

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Review

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23 pages, 1492 KiB

Open AccessReview

Switching from Apoptosis to Pyroptosis: Gasdermin-Elicited Inflammation and Antitumor Immunity

by Kohsuke Tsuchiya

Int. J. Mol. Sci. 2021, 22(1), 426; https://doi.org/10.3390/ijms22010426 - 04 Jan 2021

Cited by 146 | Viewed by 11431

Abstract

Pyroptosis is a necrotic form of regulated cell death. Gasdermines (GSDMs) are a family of intracellular proteins that execute pyroptosis. While GSDMs are expressed as inactive forms, certain proteases proteolytically activate them. The N-terminal fragments of GSDMs form pores in the plasma membrane, leading to osmotic cell lysis. Pyroptotic cells release pro-inflammatory molecules into the extracellular milieu, thereby eliciting inflammation and immune responses. Recent studies have significantly advanced our knowledge of the mechanisms and physiological roles of pyroptosis. GSDMs are activated by caspases and granzymes, most of which can also induce apoptosis in different situations, for example where the expression of GSDMs is too low to cause pyroptosis; that is, caspase/granzyme-induced apoptosis can be switched to pyroptosis by the expression of GSDMs. Pyroptosis appears to facilitate the killing of tumor cells by cytotoxic lymphocytes, and it may also reprogram the tumor microenvironment to an immunostimulatory state. Understanding pyroptosis may help the development of cancer immunotherapy. In this review article, recent findings on the mechanisms and roles of pyroptosis are introduced. The effectiveness and limitations of pyroptosis in inducing antitumor immunity are also discussed. Full article

(This article belongs to the Special Issue Molecular Mechanism of Innate and Acquired Immunity in Tissue Injury)

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