Exposure to Systemic Immunosuppressive Ultraviolet Radiation Alters T Cell Recirculation through Sphingosine-1-Phosphate

J Immunol. 2021 Sep 24:ji2001261. doi: 10.4049/jimmunol.2001261. Online ahead of print.ABSTRACTSystemic suppression of adaptive immune responses is a major way in which UV radiation contributes to skin cancer development. Immune suppression is also likely to explain how UV protects from some autoimmune diseases, such as multiple sclerosis. However, the mechanisms underlying UV-mediated systemic immune suppression are not well understood. Exposure of C57BL/6 mice to doses of UV known to suppress systemic autoimmunity led to the accumulation of cells within the skin-draining lymph nodes and away from non-skin-draining lymph nodes. Transfer of CD45.1+ cells from nonirradiated donors into CD45.2+ UV-irradiated recipients resulted in preferential accumulation of donor naive T cells and a decrease in activated T cells within skin-draining lymph nodes. A single dose of immune-suppressive UV was all that was required to cause a redistribution of naive and central memory T cells from peripheral blood to the skin-draining lymph nodes. Specifically, CD69-independent increases in sphingosine-1-phosphate (S1P) receptor 1-negative naive and central memory T cells occurred in these lymph nodes. Mass spectrometry analysis showed UV-mediated activation of sphingosine kinase 1 activity, resulting in an increase in S1P levels within the lymph nodes. Topical application of a sphingosine kinase inhibitor on the skin prior to UV irradiation eliminated the UV-induced increase in lymph node S1P and ...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Source Type: research

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J Immunol. 2021 Sep 24:ji2001261. doi: 10.4049/jimmunol.2001261. Online ahead of print.ABSTRACTSystemic suppression of adaptive immune responses is a major way in which UV radiation contributes to skin cancer development. Immune suppression is also likely to explain how UV protects from some autoimmune diseases, such as multiple sclerosis. However, the mechanisms underlying UV-mediated systemic immune suppression are not well understood. Exposure of C57BL/6 mice to doses of UV known to suppress systemic autoimmunity led to the accumulation of cells within the skin-draining lymph nodes and away from non-skin-draining lymph ...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Source Type: research
TITUSVILLE, N.J. – (March 19, 2021) – The Janssen Pharmaceutical Companies of Johnson &Johnson today announced that the U.S. Food and Drug Administration (FDA) approved PONVORY™ (ponesimod), a once-daily oral selective sphingosine-1-phosphate receptor 1 (S1P1) modulator, to treat adults with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease.1,2,3 PONVORY™ offers MS patients superior efficacy in reducing annualized relapse rates compared to an established oral therapy and a proven safety profil...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
This study shows that CA are released from periventricular and subpial regions to the cerebrospinal fluid and are present in the cervical lymph nodes, into which cerebrospinal fluid drains through the meningeal lymphatic system. We also show that CA can be phagocytosed by macrophages. We conclude that CA can act as containers that remove waste products from the brain and may be involved in a mechanism that cleans the brain. Moreover, we postulate that CA may contribute in some autoimmune brain diseases, exporting brain substances that interact with the immune system, and hypothesize that CA may contain brain markers that m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Iris Lavon1,2†, Coral Heli1†, Livnat Brill1, Hanna Charbit1,2 and Adi Vaknin-Dembinsky1* 1Department of Neurology and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 2Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel Background: The clinical course of multiple sclerosis ranges from benign with little disease progression and minimal disability, to severe disease requiring intensive medical treatment. There are no reliable circulating biomarkers fo...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: January 2019Source: Biomedicine &Pharmacotherapy, Volume 109Author(s): Zahra Payandeh, Armina Alagheband Bahrami, Reyhaneh Hoseinpoor, Yousef Mortazavi, Masoumeh Rajabibazl, Azam Rahimpour, Amir Hossein Taromchi, Saeed KhalilAbstractB-lymphocyte antigen CD20 (called CD20) is known as an activated-glycosylated phosphoprotein which is expressed on the surface of all B-cells. CD20 is involved in the regulation of trans-membrane Ca2+ conductance and also play critical roles in cell‐cycle progression during human B cell proliferation and activation. The appearance of monoclonal antibody (mAb) technology ...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
FACT: A vitamin D deficiency may result in as much as a 50 percent increased potential for diabetes. FACT: A vitamin D deficiency puts you at a higher risk for cancer, especially breast, prostate, colon, ovarian, and melanoma. VITAMIN D DEFICIENCY is a widespread phenomenon with significant implications for health. In modern society vitamin D deficiency is the rule, rather than the exception. While we can blame more severe cases of deficiency on grains, it also commonly occurs independent of grain consumption. The restoration of vitamin D levels is second only to grain elimination when considering the most powerful healthy...
Source: Wheat Belly Blog - Category: Cardiology Authors: Tags: Cancer Depression Diabetes News & Updates Undoctored Vitamin D Weight loss Source Type: blogs
Contributors : Sven Lindner ; Johannes SchulteSeries Type : Expression profiling by arrayOrganism : Homo sapiensNeuroblastoma is an embryonal tumor which originates from neural crest progenitor cells that fail to differentiate along their predefined route to sympathetic neurons or sympatho-adrenergic adrenal cells. It is the most common extracranial tumor of childhood and accounts for 15% of all childhood cancer deaths. Especially patients suffering from high grade or relapsed neuroblastoma have poor outcome in spite of aggressive treatment regimens including autologous stem cell transplantation. Those patients are in urge...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
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