scholarly journals The Clinical Significance of Programmed Death-1, Regulatory T Cells and Myeloid Derived Suppressor Cells in Patients with Nontuberculous Mycobacteria-Lung Disease

2019 ◽  
Vol 8 (5) ◽  
pp. 736 ◽  
Author(s):  
Chin-Chung Shu ◽  
Sheng-Wei Pan ◽  
Jia-Yih Feng ◽  
Jann-Yuan Wang ◽  
Yu-Jiun Chan ◽  
...  
Keyword(s):  
Lung Disease ◽  
Radiographic Progression ◽  
Cytotoxic T Lymphocyte ◽  
Nontuberculous Mycobacteria ◽  
Suppressor Cells ◽  
Treg Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Cd4 Lymphocytes

Background: Increasing expression of programmed death-1 (PD-1) in patients with nontuberculous mycobacteria lung disease (NTM-LD) has been reported, but its role in clinical characteristics and outcomes remains unclear. Methods: We enrolled 96 participants, including 46 with Mycobacterium avium complex (MAC)-LD, 23 with M. abscessus (MAB)-LD, and 27 controls. We measured expressions of PD-1, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and regulatory T (Treg) cells on CD4+ lymphocytes and myeloid-derived suppressor cells (MDSCs) and analyzed their association with clinical features and radiographic outcomes. Results: The percentage of PD-1 on CD4+(PD-1+CD4+) lymphocytes and MDSCs were higher in the MAC-LD group than the controls. There were no intergroup differences regarding CTLA-4+CD4+ lymphocytes. Higher PD-1+CD4+ lymphocytes were found in M. intracellulare- and M. avium-LD than in other MAC-LD. Positive sputum acid-fast stains and fibrocavitary radiographic lesions were correlated with elevated PD-1+CD4+ lymphocytes and Treg cells. The percentage of PD-1+CD4+ lymphocytes at the initial and 2 months of follow-up significantly predicted subsequent radiographic progression. Conclusion: As markers of immune tolerance, PD-1+CD4+ lymphocytes and MDSCs were higher in MAC-LD patients. The levels of PD-1+CD4+ and Treg cells were correlated with high mycobacteria bacilli burden in NTM-LD. Monitoring the expressions of PD-1+CD4+ lymphocytes may predict radiographic progression.

scholarly journals Programmed Death-Ligand 1 Expression Potentiates the Immune Modulatory Function Of Myeloid-Derived Suppressor Cells in Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Min-Jung Park ◽  
Jin-Ah Baek ◽  
Jeong Won Choi ◽  
Se Gwang Jang ◽  
Da-Som Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
Suppressor Cells ◽  
Treg Cells ◽  
Mrna Levels ◽  
Myeloid Derived Suppressor Cells ◽  
Programmed Death Ligand 1 ◽  
Follicular Helper ◽  
Programmed Death ◽  
Models Of Lupus

Multiple studies have explored the potential role of programmed death-ligand 1 (PD-L1) as a mediator of Myeloid-derived suppressor cells (MDSCs) effects in various cancers. However, the role PD-L1 expression in MDSCs on autoimmune disease is still largely unknown.This study was undertaken to whether MDSC expressing PD-L1 have more potent immunoregulatory activity and control autoimmunity more effectively in two murine models of lupus (MRL/lpr mice and Roquinsan/san mice). The populations of MDSC were increased in peripheral blood of lupus patients. The mRNA levels of immunosuppressive molecules were profoundly decreased in MDSCs from lupus patients and mice. Co-culture with splenocytes showed that PD-L1 expressing MDSCs from control mice expand both Treg cells and regulatory B cells more potently. Infusion of PD-L1 expressing MDSCs reduced autoantibody levels and degree of proteinuria and improved renal pathology of two animal models of lupus. Moreover, PD-L1 expressing MDSCs therapy can suppress double negative (CD4-CD8-CD3+) T cells, the major pathogenic immune cells and follicular helper T cells in MRL/lpr mice, and podocyte damage. Our results indicate PD-L1 expressing MDSCs have more potent immunoregualtory activity and ameliorate autoimmunity more profoundly. These findings suggest PD-L1 expressing MDSCs be a promising therapeutic strategy targeting systemic autoimmune diseases.

scholarly journals Immunomodulation by Inflammation during Liver and Gastrointestinal Tumorigenesis and Aging

2021 ◽  
Vol 22 (5) ◽  
pp. 2238
Author(s):  
Nao Nagai ◽  
Yotaro Kudo ◽  
Daisuke Aki ◽  
Hayato Nakagawa ◽  
Koji Taniguchi
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Antitumor Immunity ◽  
Suppressor Cells ◽  
Treg Cells ◽  
Cytotoxic T Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Age Related ◽  
Immunosuppressive Tumor Microenvironment ◽  
Pro Inflammatory Cytokines

Chronic inflammation is thought to promote tumorigenesis and metastasis by several mechanisms, such as affecting tumor cells directly, establishing a tumor-supporting microenvironment, enhancing tumor angiogenesis, and suppressing antitumor immunity. In this review, we discuss the recent advances in our understanding of how inflammation induces the immunosuppressive tumor microenvironment, such as increasing the level of pro-inflammatory cytokines, chemokines, and immunosuppressive molecules, inducing immune checkpoint molecules and cytotoxic T-cell exhaustion, and accumulating regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). The suppression of antitumor immunity by inflammation is especially examined in the liver and colorectal cancer. In addition, chronic inflammation is induced during aging and causes age-related diseases, including cancer, by affecting immunity. Therefore, we also discuss the age-related diseases regulated by inflammation, especially in the liver and colon.

scholarly journals Programmed death-1 promotes contused skeletal muscle regeneration by regulating Treg cells and macrophages

2021 ◽  
Author(s):  
Jian Shou ◽  
Xinjuan Shi ◽  
Xiaoguang Liu ◽  
Yingjie Chen ◽  
Peijie Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Macrophage Polarization ◽  
Treg Cells ◽  
Stress Factors ◽  
Skeletal Muscle Regeneration ◽  
Inflammatory Factors ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Inflammatory Macrophages

AbstractImmune cells are involved in skeletal muscle regeneration. The mechanism by which Treg cells are involved in the regeneration of injured skeletal muscle is still unclear. The purpose of this study was to explore the role of programmed death-1 in contused skeletal muscle regeneration, and to clarify the regulation of programmed death-1 on Treg cell generation and macrophage polarization, in order to deepen our understanding of the relationship between the immune system and injured skeletal muscle regeneration. The results show that programmed death-1 knockdown reduced the number of Treg cells and impaired contused skeletal muscle regeneration compared with those of wild-type mice. The number of pro-inflammatory macrophages in the contused skeletal muscle of programmed death-1 knockout mice increased, and the expression of pro-inflammatory factors and oxidative stress factors increased, while the number of anti-inflammatory macrophages and the expression of anti-inflammatory factors, antioxidant stress factors, and muscle regeneration-related factors decreased. These results suggest that programmed death-1 can promote contused skeletal muscle regeneration by regulating Treg cell generation and macrophage polarization.

scholarly journals Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)- and Programmed Death 1 (PD-1)-Mediated Regulation of Monofunctional and Dual Functional CD4+ and CD8+ T-Cell Responses in a Chronic Helminth Infection

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Anuradha Rajamanickam ◽  
Saravanan Munisankar ◽  
Chandrakumar Dolla ◽  
Thomas B. Nutman ◽  
Subash Babu
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Helminth Infection ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Content Type ◽  
Cell Responses ◽  
Dual Functional ◽  
Programmed Death ◽  
Programmed Death 1

ABSTRACT Chronic helminth infections are known to be associated with the modulation of antigen-specific T-cell responses. Strongyloides stercoralis infection is characterized by the downmodulation of antigen-specific Th1 and Th17 responses and the upregulation of Th2 and Th9 responses. Immune homeostasis is partially maintained by negative regulators of T-cell activation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), which dampen effector responses during chronic infections. However, their roles in S. stercoralis infection are yet to be defined. Therefore, we sought to determine the role of CTLA-4 and PD-1 in regulating CD4+ and CD8+ T-cell responses and examined the frequencies of monofunctional and dual functional Th1/T cytotoxic type 1 (Tc1), Th17/Tc17, Th2/Tc2, and Th9/Tc9 cells in S. stercoralis infection in 15 infected individuals stimulated with parasite antigen following CTLA-4 or PD-1 blockade. Our data reveal that CTLA-4 or PD-1 blockade results in significantly enhanced frequencies of monofunctional and dual functional Th1/Tc1 and Th17/Tc17 cells and, in contrast, diminishes the frequencies of monofunctional and dual functional Th2/Tc2 and Th9/Tc9 cells with parasite antigen stimulation in whole-blood cultures. Thus, we demonstrate that CTLA-4 and PD-1 limit the induction of particular T-cell subsets in S. stercoralis infection, which suggests the importance of CTLA-4 and PD-1 in immune modulation in a chronic helminth infection.

Myeloid‐derived suppressor cells: Roles and relations with Th2, Th17, and Treg cells in asthma

Allergy ◽  
2019 ◽  
Vol 74 (11) ◽  
pp. 2233-2237 ◽  
Author(s):  
Qingdong Guan ◽  
Bin Yang ◽  
Richard J. Warrington ◽  
Steven Mink ◽  
Chrystyna Kalicinsky ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Treg Cells ◽  
Myeloid Derived Suppressor Cells

scholarly journals A case report of psoriasis flare following immunotherapy: Report of an important entity and literature review

2020 ◽  
Vol 8 ◽  
pp. 2050313X1989770 ◽  
Author(s):  
Anastasia Politi ◽  
Dimas Angelos ◽  
Davide Mauri ◽  
George Zarkavelis ◽  
George Pentheroudakis
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Skin Lesions ◽  
Inflammatory Disorder ◽  
Immune Mediated ◽  
Programmed Death ◽  
History Of ◽  
Programmed Death 1 ◽  
Cessation Of Treatment

Immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed death-1, are a type of cancer immunotherapy approved for late-stage malignancy treatment. However, such therapies often induce immune-related adverse events. During anti-programmed death-1 blockade therapy, the most commonly reported adverse effects are skin toxicities, such as psoriasis—a chronic immune-mediated inflammatory disorder affecting the skin. We present the clinical characteristics of flared psoriasis in one patient under anti-programmed death-1 therapy who was diagnosed with T2N2M0/IIIB squamous lung carcinoma with a history of psoriasis for the past 5 years, exacerbated after the first cycle of nivolumab. After the third cycle, the extensive skin plaques necessitated treatment cessation. Following the discontinuation of anti-programmed death-1 treatment, skin lesions were treated locally. Possibly, anti-programmed death-1 immunotherapy can trigger immune-mediated diseases, such as psoriasis. Physicians should be alert to immune-related adverse events. Continuation or permanent cessation of treatment depends on the severity and reversibility of immune-related adverse events.

scholarly journals Acute kidney injury from immune checkpoint inhibitor use

2019 ◽  
Vol 12 (10) ◽  
pp. e231211 ◽  
Author(s):  
Lexis Gordon ◽  
Pouneh Dokouhaki ◽  
Kimberly Hagel ◽  
Bhanu Prasad
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Programmed Death ◽  
Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

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