scholarly journals Pro-autoimmune allele of tyrosine phosphatase, PTPN22, enhances tumor immunity

2021 ◽  
Author(s):  
Robin C Orozco ◽  
Kristi Marquardt ◽  
Kerri Mowen ◽  
Linda A Sherman
Keyword(s):  
Tumor Immunity ◽  
Immune Cells ◽  
Tumor Response ◽  
Tyrosine Phosphatase ◽  
Cd8 T Cell ◽  
North American Population ◽  
American Population ◽  
Adaptive Immune ◽  
The North ◽  
Adaptive Immune Cells

The 1858C>T allele of the tyrosine phosphatase PTPN22 (causing amino acid substitution R620W in encoded protein Lyp) is present in 5-10% of the North American population and is strongly associated with numerous autoimmune diseases. Although much research has been done to define how this allele potentiates autoimmunity, the influence PTPN22 and its pro-autoimmune allele has in tumor immunity is poorly defined. To interrogate the role this allele may have in the anti-tumor immune response, we used CRISPR/Cas9 to generate mice in which the ortholog of Lyp, PEP, is mutated at position 619 to produce the relevant pro-autoimmune mutation (R619W). Results of this study show that mice homozygous for this alteration (PEP-619WW) resist tumor growth as compared with wildtype mice. Consistent with these results, tumors from PEP-619WW mice have more CD45 infiltrates containing more activated CD8 T cell and CD4 T cells. Additionally, there are more cDC1 cells and less MDSCs in tumors from PEP-619WW mice. Interestingly, the tumor infiltrating PEP-619WW cDC1s have decreased PD-L1 expression compared to cDC1s from PEP-WT mice. Taken together, our data show that the pro-autoimmune allele of Ptpn22 drives a strong anti-tumor response in innate and adaptive immune cells resulting in superior control of tumors.

Overcoming the Hurdles of Tumor Immunity by Targeting Regulatory Pathways in Innate and Adaptive Immune Cells

2010 ◽  
Vol 16 (3) ◽  
pp. 255-267 ◽  
Author(s):  
Norberto Zwirner ◽  
Diego Croci ◽  
Carolina Domaica ◽  
Gabriel Rabinovich
Keyword(s):  
Tumor Immunity ◽  
Immune Cells ◽  
Regulatory Pathways ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Platelets: Angels and demons dancing on the immune stage. Nutrition conducts the orchestra

2020 ◽  
Vol 20 ◽  
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo
Keyword(s):  
Platelet Function ◽  
Immune Cells ◽  
Dual Role ◽  
Immune Functions ◽  
Omega 3 ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Inflammatory Processes

Background: Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. Objectives: The participation of platelets in inflammatory processes will be discussed also in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Conclusion: Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.

scholarly journals Left-Sided Sigmoid Diverticulitis Presenting as Right-Sided Thigh Abscess

2013 ◽  
Vol 97 (4) ◽  
pp. 285-287 ◽  
Author(s):  
Patrick Bates Murphy ◽  
Paul Belliveau
Keyword(s):  
Diverticular Disease ◽  
Gastrointestinal Symptoms ◽  
Sigmoid Diverticulitis ◽  
North American Population ◽  
American Population ◽  
The North ◽  
Colocutaneous Fistula ◽  
Atypical Presentations ◽  
Thigh Abscess ◽  
Uncommon Complication

Abstract Acquired diverticular disease of the colon is very common in the North American population. Atypical presentations are usually due to complications and rarely the predominant complaint may be related to an associated fistula. Thigh abscesses due to colocutaneous fistula represent an uncommon complication of sigmoid diverticulitis. In rare cases, a thigh abscess may be the only symptom, but gas in the thigh should raise the index of suspicion for bowel pathology. We report the second known case of a left-sided sigmoid diverticulitis leading to an isolated right thigh abscess with no gastrointestinal symptoms.

Chronic Fatigue Immune Dysfunction Syndrome: An Epidemic?

PEDIATRICS ◽  
1992 ◽  
Vol 89 (4) ◽  
pp. 802-803
Author(s):  
J. VAN AERDE
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Disease Control ◽  
Immune Dysfunction ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
North American Population ◽  
American Population ◽  
The North ◽  
Fatigue Syndrome ◽  
Minor Criteria

To the Editor.— Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) or Myalgic Encephalomyelitis (M.E.) is a debilitating neuroimmune disorder which is taking on epidemic proportions. Some estimates indicate that 5% of the North American population might become affected this decade. Smith et al1 confuse the symptom of "chronic fatigue" with the disease "chronic fatigue syndrome" The terminology is mixed up throughout the entire paper, but the authors clearly report on the symptom only. According to the Centers for Disease Control (CDC), the patient has to meet two major and eight minor criteria to be diagnosed with CFIDS.

scholarly journals Tuning cancer fate: the unremitting role of host immunity

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170006 ◽  
Author(s):  
B. Calì ◽  
B. Molon ◽  
A. Viola
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tumour Progression ◽  
Host Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Immune Cell Subsets ◽  
Therapeutic Protocols

Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site. This pliable interplay between immune and malignant cells is a relentless process that has been concisely organized in three different phases: elimination, equilibrium and escape. In this review, we aim to depict the distinct immune cell subsets and immune-mediated responses characterizing the tumour landscape throughout the three interconnected phases. Importantly, the identification of key immune players and molecules involved in the dynamic crosstalk between tumour and immune system has been crucial for the introduction of reliable prognostic factors and effective therapeutic protocols against cancers.

IN VIVO IMMUNOSUPPRESSIVE EFFECTS OF INTRAVENOUS IMMUNOGLOBULIN ON INNATE AND ADAPTIVE IMMUNE CELLS INVOLVED IN ALLOGRAFT REJECTION

2010 ◽  
Vol 90 ◽  
pp. 395
Author(s):  
A. S. Tjon ◽  
T. Tha-In ◽  
H. J. Metselaar ◽  
L. V.D. Laan ◽  
Z. M. Groothuismink ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Immune Cells ◽  
Allograft Rejection ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

scholarly journals The Hygiene Hypothesis and New Perspectives—Current Challenges Meeting an Old Postulate

2021 ◽  
Vol 12 ◽  
Author(s):  
Holger Garn ◽  
Daniel Piotr Potaczek ◽  
Petra Ina Pfefferle
Keyword(s):  
Immune Cells ◽  
Hygiene Hypothesis ◽  
Fine Tuning ◽  
Global Changes ◽  
Industrialized Countries ◽  
New Developments ◽  
Asthma Phenotypes ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

During its 30 years history, the Hygiene Hypothesis has shown itself to be adaptable whenever it has been challenged by new scientific developments and this is a still a continuously ongoing process. In this regard, the mini review aims to discuss some selected new developments in relation to their impact on further fine-tuning and expansion of the Hygiene Hypothesis. This will include the role of recently discovered classes of innate and adaptive immune cells that challenges the old Th1/Th2 paradigm, the applicability of the Hygiene Hypothesis to newly identified allergy/asthma phenotypes with diverse underlying pathomechanistic endotypes, and the increasing knowledge derived from epigenetic studies that leads to better understanding of mechanisms involved in the translation of environmental impacts on biological systems. Further, we discuss in brief the expansion of the Hygiene Hypothesis to other disease areas like psychiatric disorders and cancer and conclude that the continuously developing Hygiene Hypothesis may provide a more generalized explanation for health burden in highly industrialized countries also relation to global changes.

scholarly journals The impact of body mass index on adaptive immune cells in the human bone marrow

2020 ◽  
Author(s):  
Luca Pangrazzi ◽  
Erin Naismith ◽  
Carina Miggitsch ◽  
Jose’ Antonio Carmona Arana ◽  
Michael Keller ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Bone Marrow ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Immune Cells ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. The importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented in mice. Recently, some groups have investigated the survival of effector/memory T cells in the human BM. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown.Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV- and CMV+ groups.Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8+ T cells was reduced. In addition, the frequency of B cells and CD4+ T cells positively correlated with BMI in the BM of CMV- persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons.Conclusion. Our work suggests that, in addition to aging and CMV, obesity may represent an additional risk factor for immunosenescence in adaptive immune cells. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

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