Browsing by Subject "Immune system"

Now showing 1 - 4 of 4
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    Clinical characteristics and outcomes of autoimmune pancreatitis based on serum immunoglobulin G4 levels: A single-center, retrospective cohort study
    (Baishideng, 2023) Jaber, Fouad; Elfert, Khaled; Alsakarneh, Saqr; Beran, Azizullah; Jaber, Mohammed; Gangwani, Manesh Kumar; Abboud, Yazan; Medicine, School of Medicine
    Autoimmune pancreatitis (AIP) is a complex, poorly understood disease gaining increasing attention. "Clinical Characteristics and Outcome of AIP Based on Serum IgG4 levels," investigated AIP with a focus on serum immunoglobulin (Ig) G4 levels. The 213 patients with AIP were classified according to serum IgG4 levels: Abnormal (elevated) and normal. Patients with higher IgG4 levels exhibited a more active immune system and increased relapse rates. Beyond IgG4, the IgA levels and age independently contributed to relapse risk, guiding risk assessment and tailored treatments for better outcomes. However, limitations persist, such as no IgA correlation with IgG4 levels, absent data on autoantibody-positive AIP cases critical for Asian diagnostic criteria, and unexplored relapse rates in high serum IgG AIP by subtype. Genetic factors and family histories were not addressed. As the understanding and referral of seronegative AIPs increase, there's a growing need for commercially available, highly sensitive, and specific autoantibodies to aid in diagnosing individuals with low or absent serum IgG4 levels.
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    Elucidating the role of BCL6 in helper T cell activation, proliferation, and differentiation
    (2014) Hollister, Kristin N.; Dent, Alexander L.; Brutkiewicz, Randy R.; Harrington, Maureen A.; Kaplan, Mark H.
    The transcriptional repressor BCL6 has been shown to be essential for the differentiation of germinal center (GC) B cells and follicular T helper (TFH) cells. The interaction of TFH and GC B cells is necessary for the development of high affinity antibodies specific for an invading pathogen. Germline BCL6-deficient mouse models limit our ability to study BCL6 function in T cells due to the strong inflammatory responses seen in these mice. To overcome this, our lab has developed a new BCL6 conditional knockout (cKO) mouse using the cre/lox system, wherein the zinc finger region of the BCL6 gene is flanked by loxP sites. Mating to a CD4-Cre mouse allowed us to study the effects of BCL6 loss specifically in T cells, without the confounding effects seen in germline knockout models. Using this cKO model, we have reaffirmed the necessity of BCL6 for TFH differentiation, including its role in sustained CXCR5 surface expression, a signature marker for TFH cells. This model also allowed us to recognize the role of BCL6 in promoting the expression of PD-1, another key surface marker for TFH cells. Without BCL6, CD4+ T cells cannot express PD-1 at the high levels seen on TFH cells. Our discovery of DNMT3b as a target for BCL6 suggests BCL6-deficient T cells have increased DNA methyltransferase activity at the PD-1 promoter. This data establishes a novel pathway for explaining how BCL6, a transcriptional repressor, can activate genes. Experiments with the BCL6 cKO model have also established a role for BCL6 in naïve CD4+ T cell activation. Furthermore, we did not observe increased differentiation of other helper T cell subsets, in contrast to what has been reported elsewhere with germline BCL6-deficient models. Unexpectedly, we found decreased T helper type 2 (Th2) cells, whereas mouse models with a germline mutation of BCL6 have increased Th2 cells. These results indicate that BCL6 activity in non-T cells is critical for controlling T cell differentiation. Finally, using an HIV-1 gp120 immunization model, we have, for the first time, shown BCL6-dependent GCs to be limiting for antibody development and affinity maturation in a prime-boost vaccine scheme.
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    The role of the immune system in brain metastasis
    (Current Neurobiology, 2019-07) Leibold, Adam T.; Monaco, Gina N.; Dey, Mahua; Neurosurgery, IU School of Medicine
    Metastatic brain tumors are the most common brain tumors in adults. With numerous successful advancements in systemic treatment of most common cancer types, brain metastasis is becoming increasingly important in the overall prognosis of cancer patients. Brain metastasis of peripheral tumor is the result of complex interplay of primary tumor, immune system and central nervous system microenvironment. Once formed, brain metastases hide behind the blood brain barrier and become inaccessible to chemotherapies that are otherwise successful in targeting systemic cancer. The approval of immune checkpoint inhibitors for several common cancers such as advanced melanoma and lung cancers brings with it the opportunity and obligation to further understand the mechanisms of immunosuppression by tumors that spread to the brain as well as the interaction between the brain environment and tumor microenvironment. In this review paper we define the central role of the immune system in the development of brain metastases. We performed a comprehensive review of the literature to outline the molecular mechanisms of immunosuppression used by tumors and how the immune system interacts with the central nervous system to facilitate brain metastasis. In particular we discuss the tumor-type-specific mechanisms of metastasis of cancers that preferentially metastasize to the brain as well as the therapies that effectively modulate the immune response, such as immune checkpoint inhibitors and vaccines.
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    A tale of motor neurons and CD4+ T cells: moving forward by looking back
    (Wolters Kluwer, 2017-04) Iyer, Abhirami Kannan; Jones, Kathryn J.; Anatomy and Cell Biology, School of Medicine
    Amyotrophic lateral sclerosis (ALS) is a fatal progressive disorder characterized by the selective degeneration of motor neurons (MN). The impact of peripheral immune status on disease progression and MN survival is becoming increasingly recognized in the ALS research field. In this review, we briefly discuss findings from mouse models of peripheral nerve injury and immunodeficiency to understand how the immune system regulates MN survival. We extend these observations to similar studies in the widely used superoxide dismutase 1 (SOD1) mouse model of ALS. Last, we present future hypotheses to identify potential causative factors that lead to immune dysregulation in ALS. The lessons from preceding work in this area offer new exciting directions to bridge the gap in our current understanding of immune-mediated neuroprotection in ALS.