scholarly journals Innate Lymphoid Cells in Skin Homeostasis and Malignancy

2021 ◽  
Vol 12 ◽  
Author(s):  
Marek Wagner ◽  
Shigeo Koyasu
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Antigen Receptors ◽  
First Line ◽  
Adaptive Immune ◽  
Skin Malignancy ◽  
Barrier Tissues

Innate lymphoid cells (ILCs) are mostly tissue resident lymphocytes that are preferentially enriched in barrier tissues such as the skin. Although they lack the expression of somatically rearranged antigen receptors present on T and B cells, ILCs partake in multiple immune pathways by regulating tissue inflammation and potentiating adaptive immunity. Emerging evidence indicates that ILCs play a critical role in the control of melanoma, a type of skin malignancy thought to trigger immunity mediated mainly by adaptive immune responses. Here, we compile our current understanding of ILCs with regard to their role as the first line of defence against melanoma development and progression. We also discuss areas that merit further investigation. We envisage that the possibility to harness therapeutic potential of ILCs might benefit patients suffering from skin malignancies such as melanoma.

Innate Lymphoid Cells of the Lung

2019 ◽  
Vol 81 (1) ◽  
pp. 429-452 ◽  
Author(s):  
Jillian L. Barlow ◽  
Andrew N.J. McKenzie
Keyword(s):  
Immune Responses ◽  
Innate Lymphoid Cells ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Therapeutic Interventions ◽  
Antigen Receptors ◽  
Interconnected Network ◽  
Adaptive Immune ◽  
Major Organ ◽  
Ifn Γ

Although, as the major organ of gas exchange, the lung is considered a nonlymphoid organ, an interconnected network of lung-resident innate cells, including epithelial cells, dendritic cells, macrophages, and natural killer cells is crucial for its protection. These cells provide defense against a daily assault by airborne bacteria, viruses, and fungi, as well as prevent the development of cancer, allergy, and the outgrowth of commensals. Our understanding of this innate immune environment has recently changed with the discovery of a family of innate lymphoid cells (ILCs): ILC1s, ILC2s, and ILC3s. All lack adaptive antigen receptors but can provide a substantial and rapid source of IFN-γ, IL-5 and IL-13, and IL-17A or IL-22, respectively. Their ability to afford immediate protection to the lung and to influence subsequent adaptive immune responses highlights the importance of understanding ILC-regulated immunity for the design of future therapeutic interventions.

scholarly journals T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo

2020 ◽  
Author(s):  
J-H Schroeder ◽  
N Garrido-Mesa ◽  
T Zabinski ◽  
AL Gallagher ◽  
L Campbell ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Fate Mapping ◽  
Functional Roles ◽  
Mucosal Surfaces ◽  
Group 2

ABSTRACTInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Various subsets exist resembling T cell lineages defined by the expression of specific transcription factors. Thus, T-bet is expressed in ILC1 and Th1 cells. In order to further understand the functional roles of T-bet in ILC, we generated a fate-mapping mouse model that permanently marks cells and their progeny that are expressing, or have ever expressed T-bet. Here we have identified and characterised a novel ILC with characteristics of ILC1 and ILC2 that are “fate-mapped” for T-bet expression and arise early in neonatal life prior to establishment of a mature microbiome. These ILC1-ILC2 cells are critically dependent on T-bet and are able to express type 1 and type 2 cytokines at steady state, but not in the context of inflammation. These findings refine our understanding of ILC lineage regulation and stability and have important implications for the understanding of ILC biology at mucosal surfaces.SUMMARYInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Three distinct ILC groups have been described according to expression of subset defining transcription factors and other markers. In this study we characterize a novel ILC subset with characteristics of group 1 and group 2 ILC in vivo.

scholarly journals Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Abbas Pishdadian ◽  
Abdol-Reza Varasteh ◽  
Mojtaba Sankian
Keyword(s):  
Allergic Inflammation ◽  
Innate Lymphoid Cells ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Antigen Receptors ◽  
First Line ◽  
Innate And Adaptive Immunity ◽  
Type 2 Cytokines

Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 “immune franchise.” Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma.

scholarly journals Rapamycin Alternatively Modifies Mitochondrial Dynamics in Dendritic Cells to Reduce Kidney Ischemic Reperfusion Injury

2021 ◽  
Vol 22 (10) ◽  
pp. 5386
Author(s):  
Maria Namwanje ◽  
Bijay Bisunke ◽  
Thomas V. Rousselle ◽  
Gene G. Lamanilao ◽  
Venkatadri S. Sunder ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Mitochondrial Dynamics ◽  
Graft Loss ◽  
Kidney Injury ◽  
Adaptive Immune ◽  
Consumption Rates ◽  
Regulatory Phenotype

Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with rapamycin (10 ng/mL) for 1 h before LPS. In contrast, rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of rapamycin-treated DCs to WT recipients 24 h before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/mL) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.

scholarly journals IN LABORATORY GENERATION AND MATURATION OF HUMAN MONOCYTE-DERIVED DENDRITIC CELLS FOR CANCER IMMUNOTHERAPY

2020 ◽  
pp. 46-52
Author(s):  
KANCHAN K. MISHRA ◽  
SUMIT BHARADVA ◽  
MEGHNAD G. JOSHI ◽  
ARVIND GULBAKE
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Gradient Centrifugation ◽  
Critical Role ◽  
Human Monocyte ◽  
Blood Monocytes ◽  
Adaptive Immune ◽  
Immunodeficiency Virus ◽  
Adaptive Immune Systems

Dendritic cells (DCs) play a critical role in the regulation of adaptive immune responses, furthermore they act as a bridge between the innate and the adaptive immune systems they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. The first reported trial using DCs in 1995, since they have been used in trials all over the world for several of indications, including cancer and human immunodeficiency virus infection. Generally, for in vitro experiments or for DCs vaccination monocyte-derived dendritic cells (moDCs) were generated from purified monocytes that isolated from peripheral blood by density gradient centrifugation. A variety of methods can be used for enrichment of monocytes for generation of clinical-grade DCs. Herein we summarized up to date understanding of systems and inputs used in procedures to differentiate DCs from blood monocytes in vitro.

scholarly journals Innate immunity and the pneumococcus

Microbiology ◽  
2006 ◽  
Vol 152 (2) ◽  
pp. 285-293 ◽  
Author(s):  
Gavin K. Paterson ◽  
Tim J. Mitchell
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Innate Immune System ◽  
Innate Immune ◽  
First Line ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Made In

The innate immune system provides a non-specific first line of defence against microbes and is crucial both in the development and effector stages of subsequent adaptive immune responses. Consistent with its importance, study of the innate immune system is a broad and fast-moving field. Here we provide an overview of the recent key advances made in this area with relation to the important pathogen Streptococcus pneumoniae (the pneumococcus).

scholarly journals STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Tang ◽  
Sanda A. Tan ◽  
Atif Iqbal ◽  
Jian Li ◽  
Sarah C. Glover
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Immune Responses ◽  
Tyrosine Phosphorylation ◽  
Innate Lymphoid Cells ◽  
Immune Defense ◽  
Lymphoid Cells ◽  
Dependent Manner ◽  
Regulatory Pathways ◽  
Innate Effector

Crohn’s disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in a cell-specific, cytokine-dependent manner, involving multiple immune responses. This study proposes the positive correlation between the prevalence of STAT3 rs744166 risky allele “A” with the severity of disease in a cohort of 94 CD patients. In addition, the results suggest an increased STAT3 activity in the inflamed ileum of CD patients, compared to unaffected ileum sections. Notably, IL-23 triggers the differentiation of CD117+NKp44- ILC3s and induces the activation of STAT3 in both CD117+NKp44- and CD117-NKp44- ILC subsets, implying the involvement of STAT3 in the initiation of ILC plasticity. Moreover, carriage of STAT3 “A” risk allele exhibited a higher basal level of STAT3 tyrosine phosphorylation, and an increased IL-23 triggered the pSTAT3 level. We also demonstrated that there was no delayed dephosphorylation of STAT3 in ILCs of both A/A and G/G donors. Overall, the results of this study suggest that IL-23-induced activation of STAT3 in the CD117-NKp44- ILC1s involves in ILC1-to-ILC3 plasticity and a potential regulatory role of ILC1 function. Those genetically susceptible individuals carried STAT3 rs744166 risky allele appear to have higher basal and cytokine-stimulated activation of STAT3 signal, leading to prolonged inflammation and chronic relapse.

scholarly journals CD4 T Helper Cell Subsets and Related Human Immunological Disorders

2020 ◽  
Vol 21 (21) ◽  
pp. 8011 ◽  
Author(s):  
Xiaoliang Zhu ◽  
Jinfang Zhu
Keyword(s):  
Transcription Factor ◽  
Immune System ◽  
Immune Responses ◽  
Critical Role ◽  
Cell Subset ◽  
Lymphoid Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Th2 Cells ◽  
T Helper

The immune system plays a critical role in protecting hosts from the invasion of organisms. CD4 T cells, as a key component of the immune system, are central in orchestrating adaptive immune responses. After decades of investigation, five major CD4 T helper cell (Th) subsets have been identified: Th1, Th2, Th17, Treg (T regulatory), and Tfh (follicular T helper) cells. Th1 cells, defined by the expression of lineage cytokine interferon (IFN)-γ and the master transcription factor T-bet, participate in type 1 immune responses to intracellular pathogens such as mycobacterial species and viruses; Th2 cells, defined by the expression of lineage cytokines interleukin (IL)-4/IL-5/IL-13 and the master transcription factor GAΤA3, participate in type 2 immune responses to larger extracellular pathogens such as helminths; Th17 cells, defined by the expression of lineage cytokines IL-17/IL-22 and the master transcription factor RORγt, participate in type 3 immune responses to extracellular pathogens including some bacteria and fungi; Tfh cells, by producing IL-21 and expressing Bcl6, help B cells produce corresponding antibodies; whereas Foxp3-expressing Treg cells, unlike Th1/Th2/Th17/Tfh exerting their effector functions, regulate immune responses to maintain immune cell homeostasis and prevent immunopathology. Interestingly, innate lymphoid cells (ILCs) have been found to mimic the functions of three major effector CD4 T helper subsets (Th1, Th2, and Th17) and thus can also be divided into three major subsets: ILC1s, ILC2s, and ILC3s. In this review, we will discuss the differentiation and functions of each CD4 T helper cell subset in the context of ILCs and human diseases associated with the dysregulation of these lymphocyte subsets particularly caused by monogenic mutations.

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