During their lives, cells encounter several types of stresses in response to which they have evolved different defense mechanisms. Depending on the kind of stress and cell type, injured cells have different fates, such as autophagy, cellular senescence, or different types of regulated cell death (RCD) such as apoptosis, necroptosis, ferroptosis, pyroptosis, NETotic cell death, and immunogenic cell death (ICD). These stresses have been shown to induce an immune reaction as an attempt to restore tissue homeostasis, linking intra-cellular signals to inter-cellular responses. Indeed, stressed cells are able to stimulate the immune system via the active or passive release of soluble factors, which include cytokines (e.g. IL-1b, TNF, IL-6, type I IFN, CXCL10, CCL2), metabolic intermediates (e.g. ATP), nucleic acids, intracellular proteins (e.g. HMGB1, ANXA1), ER chaperons (e.g. CALR, HSPs), or microvesicles, and/or the surface expression of stress-induced molecules (e.g. MHC class I molecules, ligands of NK cell-activating receptors). In turn, cells of the innate and adaptive immune system promote tissue repair by eliminating damaged or unwanted cells and changing the cytokine milieu. However, the way the immune system recognizes and deals with stressed cells remains unclear, and pathological conditions, such as chronic inflammation, may lead to tissue integrity breaking, autoimmunity, and cancer. In this context, cellular senescence represents a paradigm, as the senescence-associated secretory phenotype (SASP) that is strictly associated with senescent cells can induce “acute” as well as “chronic” immune responses, leading to opposite results: either tissue rejuvenation or aging. Indeed, the SASP composition encompasses cytokines, chemokines, growth factors, and proteases and, in this way, senescent cells together with immune cells participate in tissue remodeling during embryogenesis, wound healing, and cancer.
This Research Topic aims at discussing immune cell stress sensing through various receptors including PRRs, cytokines and NK cell receptors. Moreover, it focuses on how these stresses are triggered to support systemic homeostasis but also paving the way to maladaptation and disease. We welcome authors to submit Original Research or Review articles that cover the following subtopics:
- Recruitment and activation of local and systemic innate and adaptive immune cells after different types of cellular stresses, including those triggering the DNA damage response, (e.g. ionizing radiation, genotoxic drugs), the unfolded protein response, (e.g. some chemotherapeutic agents), the mitochondrial stress signaling (e.g. ROS), and autophagy (e.g. caloric restriction).
- Molecular pathways that make stressed cells visible to the immune system, such as the NKG2D/NKG2D ligands axis
- Pharmacological approaches that can enhance/modulate the immune surveillance of stressed cells (e.g. immunomodulatory drugs, senotherapy)
- How the SASP drives inflammation and shape tissue microenvironment
- Regulation of tissue microenvironment in terms of cytokines and growth factors produced by cells of the innate and adaptive immune system in response to stress
- Tissue remodeling during acute/prolonged, local/systemic inflammation: for example, the liver fibrosis after hepatic damage and subsequent NK cell recruitment, endometrial remodeling by NK cell-mediated clearance of senescent decidual cells, chronic inflammation and/or fibrosis induced by multiple molecules including extracellular matrix modifying proteases
During their lives, cells encounter several types of stresses in response to which they have evolved different defense mechanisms. Depending on the kind of stress and cell type, injured cells have different fates, such as autophagy, cellular senescence, or different types of regulated cell death (RCD) such as apoptosis, necroptosis, ferroptosis, pyroptosis, NETotic cell death, and immunogenic cell death (ICD). These stresses have been shown to induce an immune reaction as an attempt to restore tissue homeostasis, linking intra-cellular signals to inter-cellular responses. Indeed, stressed cells are able to stimulate the immune system via the active or passive release of soluble factors, which include cytokines (e.g. IL-1b, TNF, IL-6, type I IFN, CXCL10, CCL2), metabolic intermediates (e.g. ATP), nucleic acids, intracellular proteins (e.g. HMGB1, ANXA1), ER chaperons (e.g. CALR, HSPs), or microvesicles, and/or the surface expression of stress-induced molecules (e.g. MHC class I molecules, ligands of NK cell-activating receptors). In turn, cells of the innate and adaptive immune system promote tissue repair by eliminating damaged or unwanted cells and changing the cytokine milieu. However, the way the immune system recognizes and deals with stressed cells remains unclear, and pathological conditions, such as chronic inflammation, may lead to tissue integrity breaking, autoimmunity, and cancer. In this context, cellular senescence represents a paradigm, as the senescence-associated secretory phenotype (SASP) that is strictly associated with senescent cells can induce “acute” as well as “chronic” immune responses, leading to opposite results: either tissue rejuvenation or aging. Indeed, the SASP composition encompasses cytokines, chemokines, growth factors, and proteases and, in this way, senescent cells together with immune cells participate in tissue remodeling during embryogenesis, wound healing, and cancer.
This Research Topic aims at discussing immune cell stress sensing through various receptors including PRRs, cytokines and NK cell receptors. Moreover, it focuses on how these stresses are triggered to support systemic homeostasis but also paving the way to maladaptation and disease. We welcome authors to submit Original Research or Review articles that cover the following subtopics:
- Recruitment and activation of local and systemic innate and adaptive immune cells after different types of cellular stresses, including those triggering the DNA damage response, (e.g. ionizing radiation, genotoxic drugs), the unfolded protein response, (e.g. some chemotherapeutic agents), the mitochondrial stress signaling (e.g. ROS), and autophagy (e.g. caloric restriction).
- Molecular pathways that make stressed cells visible to the immune system, such as the NKG2D/NKG2D ligands axis
- Pharmacological approaches that can enhance/modulate the immune surveillance of stressed cells (e.g. immunomodulatory drugs, senotherapy)
- How the SASP drives inflammation and shape tissue microenvironment
- Regulation of tissue microenvironment in terms of cytokines and growth factors produced by cells of the innate and adaptive immune system in response to stress
- Tissue remodeling during acute/prolonged, local/systemic inflammation: for example, the liver fibrosis after hepatic damage and subsequent NK cell recruitment, endometrial remodeling by NK cell-mediated clearance of senescent decidual cells, chronic inflammation and/or fibrosis induced by multiple molecules including extracellular matrix modifying proteases
