scholarly journals 131 CLADIN: CLADribine and INnate immune responses

2019 ◽  
Vol 90 (e7) ◽  
pp. A42.3-A42
Author(s):  
Mastura Monif ◽  
Shokoufeh Abdollahi ◽  
Jim Stankovich ◽  
Vicki Maltby ◽  
Jeannette Lechner-Scott ◽  
...  
Keyword(s):  
Clinical Data ◽  
Immune Cells ◽  
Purinergic Receptor ◽  
Oral Treatment ◽  
Clinical Care ◽  
Brain Mri ◽  
Critical Role ◽  
Laboratory Data ◽  
Innate Immune ◽  
Innate Immune Cells

IntroductionCladribine Tablets (Mavenclad®) is nucleoside analogue of deoxyadenosine, and an oral treatment for relapsing remitting MS (RRMS). In RRMS clinical trials, Cladribine has been shown to reduce brain atrophy, relapse rates, and new lesions on brain MRI. P2X7R is a purinergic receptor expressed in innate immune cells, and is thought to play a critical role in neuroinflammation. The mechanism of action of Cladribine on peripheral innate immune cells (monocytes), and its effect on P2X7R, is unclear, and forms the basis of this study.MethodsThis will be a Phase IV, multi-centre, 3 year, translational trial. Patients who are starting Cladribine as part of their routine clinical care will consent to take part in the study. Monocyte numbers and activation states will be measured at various times prior and after commencement of therapy. In addition, and in an in vitro setting the effect of Cladribine on P2X7R expression and function will be assessed, as well as measuring various cytokines/chemokines in serum. The laboratory data will also be correlated with clinical data from another long-term Cladribine study, CLOBAS.ResultsThis study has been approved by Alfred Health Human Research Ethics Committee. The study is to commence in April 2019.ConclusionThis study will shed light on whether Cladribine is exerting its beneficial effects via action on peripheral monocytes and alterations of their P2X7Rs. The laboratory and clinical data will be analysed to understand the relationship between innate immune parameters and patient outcome.

scholarly journals A critical role for pannexin-1 in activation of innate immune cells of the choroid plexus

Channels ◽  
2014 ◽  
Vol 8 (2) ◽  
pp. 131-141 ◽  
Author(s):  
Valentyna Maslieieva ◽  
Roger J Thompson
Keyword(s):  
Choroid Plexus ◽  
Immune Cells ◽  
Critical Role ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Pannexin 1

scholarly journals A Critical Role for the TLR4/TRIF Pathway in Allogeneic Hematopoietic Cell Rejection by Innate Immune Cells

2013 ◽  
Vol 22 (12) ◽  
pp. 2367-2380 ◽  
Author(s):  
Hong Xu ◽  
Jun Yan ◽  
Ziqiang Zhu ◽  
Lala-Rukh Hussain ◽  
Yiming Huang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Critical Role ◽  
Innate Immune ◽  
Hematopoietic Cell ◽  
Innate Immune Cells

scholarly journals Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design

2016 ◽  
Vol 241 (10) ◽  
pp. 1084-1097 ◽  
Author(s):  
Molly E Ogle ◽  
Claire E Segar ◽  
Sraeyes Sridhar ◽  
Edward A Botchwey
Keyword(s):  
Inflammatory Response ◽  
Immune Cells ◽  
Tissue Repair ◽  
Tissue Injury ◽  
Critical Role ◽  
Myeloid Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Signaling Systems ◽  
Monocytes And Macrophages

Monocytes and macrophages play a critical role in tissue development, homeostasis, and injury repair. These innate immune cells participate in guiding vascular remodeling, stimulation of local stem and progenitor cells, and structural repair of tissues such as muscle and bone. Therefore, there is a great interest in harnessing this powerful endogenous cell source for therapeutic regeneration through immunoregenerative biomaterial engineering. These materials seek to harness specific subpopulations of monocytes/macrophages to promote repair by influencing their recruitment, positioning, differentiation, and function within a damaged tissue. Monocyte and macrophage phenotypes span a continuum of inflammatory (M1) to anti-inflammatory or pro-regenerative cells (M2), and their heterogeneous functions are highly dependent on microenvironmental cues within the injury niche. Increasing evidence suggests that division of labor among subpopulations of monocytes and macrophages could allow for harnessing regenerative functions over inflammatory functions of myeloid cells; however, the complex balance between necessary functions of inflammatory versus regenerative myeloid cells remains to be fully elucidated. Historically, biomaterial-based therapies for promoting tissue regeneration were designed to minimize the host inflammatory response; although, recent appreciation for the roles that innate immune cells play in tissue repair and material integration has shifted this paradigm. A number of opportunities exist to exploit known signaling systems of specific populations of monocytes/macrophages to promote repair and to better understand the biological and pathological roles of myeloid cells. This review seeks to outline the characteristics of distinct populations of monocytes and macrophages, identify the role of these cells within diverse tissue injury niches, and offer design criteria for immunoregenerative biomaterials given the intrinsic inflammatory response to their implantation.

scholarly journals Apocynin, a Low Molecular Oral Treatment for Neurodegenerative Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Bert A. ‘t Hart ◽  
Sjef Copray ◽  
Ingrid Philippens
Keyword(s):  
Neurodegenerative Disease ◽  
Immune Cells ◽  
Low Dose ◽  
Therapeutic Potential ◽  
Oral Treatment ◽  
Selective Inhibitor ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Phagocyte Nadph Oxidase ◽  
Jatropha Multifida

Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases. This may imply that patients affected by a neurodegenerative disease may benefit from treatment with selective inhibitors of innate immune activity. Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plantJatropha multifida. Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose.

scholarly journals Induction of Tumor-specific T Cell Immunity by Anti-DR5 Antibody Therapy

2004 ◽  
Vol 199 (4) ◽  
pp. 437-448 ◽  
Author(s):  
Kazuyoshi Takeda ◽  
Noriko Yamaguchi ◽  
Hisaya Akiba ◽  
Yuko Kojima ◽  
Yoshihiro Hayakawa ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Critical Role ◽  
Innate Immune ◽  
Tumor Rejection ◽  
T Cell Immunity ◽  
Innate Immune Cells ◽  
Antitumor Effects ◽  
Cell Immunity

Because tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cells and plays a critical role in tumor surveillance, its receptor is an attractive target for antibody-mediated tumor therapy. Here we report that a monoclonal antibody (mAb) against the mouse TRAIL receptor, DR5, exhibited potent antitumor effects against TRAIL-sensitive tumor cells in vivo by recruiting Fc receptor–expressing innate immune cells, with no apparent systemic toxicity. Administration of the agonistic anti-DR5 mAb also significantly inhibited experimental and spontaneous tumor metastases. Notably, the anti-DR5 mAb-mediated tumor rejection by innate immune cells efficiently evoked tumor-specific T cell immunity that could also eradicate TRAIL-resistant variants. These results suggested that the antibody-based therapy targeting DR5 is an efficient strategy not only to eliminate TRAIL-sensitive tumor cells, but also to induce tumor-specific T cell memory that affords a long-term protection from tumor recurrence.

scholarly journals A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Shigetoshi Yokoyama ◽  
Yan Cai ◽  
Miyuki Murata ◽  
Takeshi Tomita ◽  
Mitsuhiro Yoneda ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Immune Cells ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Innate Immune ◽  
Cell Surface Receptor ◽  
Innate Immune Cells ◽  
Surface Receptor

Intracellular lipopolysaccharide (LPS) triggers the non-canonical inflammasome pathway, resulting in pyroptosis of innate immune cells. In addition to its well-known proinflammatory role, LPS can directly cause regression of some tumors, although the underlying mechanism has remained unknown. Here we show that secretoglobin(SCGB)3A2, a small protein predominantly secreted in airways, chaperones LPS to the cytosol through the cell surface receptor syndecan-1; this leads to pyroptotic cell death driven by caspase-11. SCGB3A2 and LPS co-treatment significantly induced pyroptosis of macrophage RAW264.7 cells and decreased cancer cell proliferation in vitro, while SCGB3A2 treatment resulted in reduced progression of xenograft tumors in mice. These data suggest a conserved function for SCGB3A2 in the innate immune system and cancer cells. These findings demonstrate a critical role for SCGB3A2 as an LPS delivery vehicle; they reveal one mechanism whereby LPS enters innate immune cells leading to pyroptosis, and they clarify the direct effect of LPS on cancer cells.

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