scholarly journals Nrf2 Is Crucial to Graft Survival in a Rodent Model of Heart Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Wu ◽  
Quan Qiu ◽  
Huihui Wang ◽  
Samantha A. Whitman ◽  
Deyu Fang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transcription Factor ◽  
Immune Responses ◽  
Graft Survival ◽  
Immune Cells ◽  
Mrna Levels ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Survival Pathways ◽  
Patients With Heart Failure

Currently, the sole treatment option for patients with heart failure is transplantation. The battle of prolonging graft survival and modulating innate and adaptive immune responses is still being waged in the clinic and in research labs. The transcription factor Nrf2 controls major cell survival pathways and is central to moderating inflammation and immune responses. In this study the effect of Nrf2 levels in host recipient C57BL/6 mice on Balb/c allogeneic graft survival was examined. Importantly, Nrf2−/−recipient mice could not support the graft for longer than 7.5 days on average, whereas activation of Nrf2 by sulforaphane in Nrf2+/+hosts prolonged graft survival to 13 days. Several immune cells in the spleen of recipient mice were unchanged; however, CD11b+macrophages were significantly increased in Nrf2−/−mice. In addition, IL-17 mRNA levels were elevated in grafts transplanted into Nrf2−/−mice. Although Nrf2 appears to play a crucial role in graft survival, the exact mechanism is yet to be fully understood.

scholarly journals Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Qin Zhao ◽  
Miusi Shi ◽  
Chengcheng Yin ◽  
Zifan Zhao ◽  
Jinglun Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
T Cell Response ◽  
Dual Wavelength ◽  
M2 Macrophage ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

AbstractThe immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.

scholarly journals The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Lan Kang ◽  
Xiang Zhang ◽  
Liangliang Ji ◽  
Tiantian Kou ◽  
Sinead M. Smith ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Late Phase ◽  
Intestinal Immunity ◽  
Adaptive Immune Responses ◽  
Cell Lineages ◽  
Adaptive Immune ◽  
Intestinal Macrophage ◽  
Pathogen Clearance

Macrophages play pleiotropic roles in maintaining the balance between immune tolerance and inflammatory responses in the gut. Here, we identified transcription factor RBP-J as a crucial regulator of colonic macrophage–mediated immune responses against the enteric pathogen Citrobacter rodentium. In the immune response phase, RBP-J promoted pathogen clearance by enhancing intestinal macrophage-elicited Th17 cell immune responses, which was achieved by maintenance of C/EBPβ-dependent IL-6 production by overcoming miRNA-17∼92–mediated suppressive effects. RBP-J deficiency–associated phenotypes could be genetically corrected by further deleting miRNA-17∼92 in macrophages. In the late phase, noneradicated pathogens in RBP-J KO mice recruited abundant IL-1β–expressing CD64+Ly6C+ colonic macrophages and thereby promoted persistence of ILC3-derived IL-22 to compensate for the impaired innate and adaptive immune responses, leading to ultimate clearance of pathogens. These results demonstrated that colonic macrophage–intrinsic RBP-J dynamically orchestrates intestinal immunity against pathogen infections by interfacing with key immune cells of T and innate lymphoid cell lineages.

scholarly journals Lactate-Dependent Regulation of Immune Responses by Dendritic Cells and Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Indumathi Manoharan ◽  
Puttur D. Prasad ◽  
Muthusamy Thangaraju ◽  
Santhakumar Manicassamy
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Adaptive Immune Responses ◽  
Effector Functions ◽  
Tissue Microenvironment ◽  
Adaptive Immune ◽  
Pathological Conditions ◽  
Recent Advances ◽  
Adaptive Immune Cells

For decades, lactate has been considered an innocuous bystander metabolite of cellular metabolism. However, emerging studies show that lactate acts as a complex immunomodulatory molecule that controls innate and adaptive immune cells’ effector functions. Thus, recent advances point to lactate as an essential and novel signaling molecule that shapes innate and adaptive immune responses in the intestine and systemic sites. Here, we review these recent advances in the context of the pleiotropic effects of lactate in regulating diverse functions of immune cells in the tissue microenvironment and under pathological conditions.

scholarly journals The Role of the Inflammatory Response in Mediating Functional Recovery Following Composite Tissue Injuries

2021 ◽  
Vol 22 (24) ◽  
pp. 13552
Author(s):  
Naveena B. Janakiram ◽  
Michael S. Valerio ◽  
Stephen M. Goldman ◽  
Christopher L. Dearth
Keyword(s):  
Wound Healing ◽  
Immune Responses ◽  
Immune Cells ◽  
Military Service ◽  
Adaptive Immune Responses ◽  
Impaired Wound Healing ◽  
Composite Tissue ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Tissue Injuries

Composite tissue injuries (CTI) are common among US Military Service members during combat operations, and carry a high potential of morbidity. Furthermore, CTI are often complicated due to an altered wound healing response, resulting in part from a dysregulation of the innate and adaptive immune responses. Unlike normal wound healing, in CTI, disruptions occur in innate immune responses, altering neutrophil functions, macrophage activation and polarization, further impacting the functions of T regulatory cells. Additionally, the biological underpinnings of these unfavorable wound healing conditions are multifactorial, including various processes, such as: ischemia, hypoxia, low nutrient levels, and altered cell metabolic pathways, among others, all of which are thought to trigger anergy in immune cells and destabilize adaptive immune responses. As a result, impaired wound healing is common in CTI. Herein, we review the altered innate and adaptive immune cells and their metabolic status and responses following CTI, and discuss the role a multi-pronged immunomodulatory approach may play in facilitating improved outcomes for afflicted patients.

scholarly journals Organization of the Skin Immune System and Compartmentalized Immune Responses in Infectious Diseases

2019 ◽  
Vol 32 (4) ◽  
Author(s):  
Juarez Antonio Simões Quaresma
Keyword(s):  
Immune System ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Immune Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Skin Immune System ◽  
Host Pathogen ◽  
Cellular Mediators ◽  
And Control

SUMMARY The skin is an organ harboring several types of immune cells that participate in innate and adaptive immune responses. The immune system of the skin comprises both skin cells and professional immune cells that together constitute what is designated skin-associated lymphoid tissue (SALT). In this review, I extensively discuss the organization of SALT and the mechanisms involved in its responses to infectious diseases of the skin and mucosa. The nature of these SALT responses, and the cellular mediators involved, often determines the clinical course of such infections. I list and describe the components of innate immunity, such as the roles of the keratinocyte barrier and of inflammatory and natural killer cells. I also examine the mechanisms involved in adaptive immune responses, with emphasis on new cytokine profiles, and the role of cell death phenomena in host-pathogen interactions and control of the immune responses to infectious agents. Finally, I highlight the importance of studying SALT in order to better understand host-pathogen relationships involving the skin and detail future directions in the immunological investigation of this organ, especially in light of recent findings regarding the skin immune system.

scholarly journals Role of Histamine in Modulating the Immune Response and Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Anna Cláudia Calvielli Castelo Branco ◽  
Fábio Seiti Yamada Yoshikawa ◽  
Anna Julia Pietrobon ◽  
Maria Notomi Sato
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Mediators ◽  
Pleiotropic Effect ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Regulatory Functions ◽  
Proinflammatory Factors

Inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, and leukotrienes, impact the immune system, usually as proinflammatory factors. Other mediators act as regulatory components to establish homeostasis after injury or prevent the inflammatory process. Histamine, a biogenic vasoactive amine, causes symptoms such as allergies and has a pleiotropic effect that is dependent on its interaction with its four histamine receptors. In this review, we discuss the dualistic effects of histamine: how histamine affects inflammation of the immune system through the activation of intracellular pathways that induce the production of inflammatory mediators and cytokines in different immune cells and how histamine exerts regulatory functions in innate and adaptive immune responses. We also evaluate the interactions between these effects.

scholarly journals The Ontogeny of a Neutrophil: Mechanisms of Granulopoiesis and Homeostasis

2018 ◽  
Vol 82 (1) ◽  
Author(s):  
Shelley M. Lawrence ◽  
Ross Corriden ◽  
Victor Nizet
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Transcriptional Regulators ◽  
Vital Role ◽  
Adaptive Immune Responses ◽  
Hematopoietic Stem ◽  
Adaptive Immune ◽  
Segmented Neutrophil ◽  
Large Numbers ◽  
Initial Appearance

SUMMARYComprising the majority of leukocytes in humans, neutrophils are the first immune cells to respond to inflammatory or infectious etiologies and are crucial participants in the proper functioning of both innate and adaptive immune responses. From their initial appearance in the liver, thymus, and spleen at around the eighth week of human gestation to their generation in large numbers in the bone marrow at the end of term gestation, the differentiation of the pluripotent hematopoietic stem cell into a mature, segmented neutrophil is a highly controlled process where the transcriptional regulators C/EBP-α and C/EBP-ε play a vital role. Recent advances in neutrophil biology have clarified the life cycle of these cells and revealed striking differences between neonatal and adult neutrophils based on fetal maturation and environmental factors. Here we detail neutrophil ontogeny, granulopoiesis, and neutrophil homeostasis and highlight important differences between neonatal and adult neutrophil populations.

scholarly journals B Cell Immunosenescence

2020 ◽  
Vol 36 (1) ◽  
pp. 551-574 ◽  
Author(s):  
Daniela Frasca ◽  
Alain Diaz ◽  
Maria Romero ◽  
Denisse Garcia ◽  
Bonnie B. Blomberg
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Immune Cells ◽  
Cell Function ◽  
Current Knowledge ◽  
The Elderly ◽  
Low Grade ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
B Cell Function

Innate and adaptive immune responses decline with age, leading to greater susceptibility to infectious diseases and reduced responses to vaccines. Diseases are more severe in old than in young individuals and have a greater impact on health outcomes such as morbidity, disability, and mortality. Aging is characterized by increased low-grade chronic inflammation, so-called inflammaging, that represents a link between changes in immune cells and a number of diseases and syndromes typical of old age. In this review we summarize current knowledge on age-associated changes in immune cells with special emphasis on B cells, which are more inflammatory and less responsive to infections and vaccines in the elderly. We highlight recent findings on factors and pathways contributing to inflammaging and how these lead to dysfunctional immune responses. We summarize recent published studies showing that adipose tissue, which increases in size with aging, contributes to inflammaging and dysregulated B cell function.

scholarly journals Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5

2018 ◽  
Vol 215 (11) ◽  
pp. 2901-2918 ◽  
Author(s):  
Maria Buxadé ◽  
Hector Huerga Encabo ◽  
Marta Riera-Borrull ◽  
Lucía Quintana-Gallardo ◽  
Pilar López-Cotarelo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
T Lymphocyte ◽  
Cell Type ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Cell Type Specific ◽  
Antigen Presenting ◽  
Mhcii Expression

MHCII in antigen-presenting cells (APCs) is a key regulator of adaptive immune responses. Expression of MHCII genes is controlled by the transcription coactivator CIITA, itself regulated through cell type–specific promoters. Here we show that the transcription factor NFAT5 is needed for expression of Ciita and MHCII in macrophages, but not in dendritic cells and other APCs. NFAT5-deficient macrophages showed defective activation of MHCII-dependent responses in CD4+ T lymphocytes and attenuated capacity to elicit graft rejection in vivo. Ultrasequencing analysis of NFAT5-immunoprecipitated chromatin uncovered an NFAT5-regulated region distally upstream of Ciita. This region was required for CIITA and hence MHCII expression, exhibited NFAT5-dependent characteristics of active enhancers such as H3K27 acetylation marks, and required NFAT5 to interact with Ciita myeloid promoter I. Our results uncover an NFAT5-regulated mechanism that maintains CIITA and MHCII expression in macrophages and thus modulates their T lymphocyte priming capacity.

Antigen presentation and adaptive immune responses in skin

2019 ◽  
Vol 31 (7) ◽  
pp. 423-429 ◽  
Author(s):  
Tetsuya Honda ◽  
Gyohei Egawa ◽  
Kenji Kabashima
Keyword(s):  
Immune Responses ◽  
Antigen Presentation ◽  
Immune Cells ◽  
Adaptive Immune Response ◽  
Short Review ◽  
Contact Hypersensitivity ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Draining Lymph Nodes

Abstract For the induction of adequate cutaneous immune responses, the antigen presentation and recognition that occur in both the skin and skin-draining lymph nodes are essential. In each process of cutaneous immune responses, several distinct subsets of immune cells, including dendritic cells and T cells, are involved, and they elicit their respective functions in a harmonious manner. For example, in the elicitation phase of cutaneous acquired immunity, immune cells form a specific lymphoid structure named inducible skin-associated lymphoid tissue (iSALT) to facilitate efficient antigen presentation in situ. In this short review, we will overview the mechanisms of how antigens are presented and how cutaneous adaptive immune responses are conducted in the skin, especially focusing on contact hypersensitivity, a prototypic adaptive immune response in the skin.

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