Low dose rapamycin exacerbates autoimmune experimental uveitis.

PloS One
Zili ZhangJames T Rosenbaum

Abstract

Rapamycin, a potent immune modulator, is used to treat transplant rejection and some autoimmune diseases. Uveitis is a potentially severe inflammatory eye disease, and 2 clinical trials of treating uveitis with rapamycin are under way. Unexpectedly, recent research has demonstrated that low dose rapamycin enhances the memory T cell population and function. However, it is unclear how low dose rapamycin influences the immune response in the setting of uveitis. B10.RIII mice were immunized to induce experimental autoimmune uveitis (EAU). Ocular inflammation of control and rapamycin-treated mice was compared based on histological change. ELISPOT and T cell proliferation assays were performed to assess splenocyte response to ocular antigen. In addition, we examined the effect of rapamycin on activation-induced cell death (AICD) using the MitoCapture assay and Annexin V staining. Administration of low dose rapamycin exacerbated EAU, whereas treating mice with high dose rapamycin attenuated ocular inflammation. The progression of EAU by low dose rapamycin coincided with the increased frequency of antigen-reactive lymphocytes. Lastly, fewer rapamycin-treated T cells underwent AICD, which might contribute to exaggerated ocular inflammat...Continue Reading

References

Jan 1, 1995·The Journal of Experimental Medicine·M R AldersonD H Lynch
Apr 15, 1999·Seminars in Cancer Biology·B T Spear
Jun 19, 2001·Current Opinion in Immunology·R C Budd
Jan 28, 2003·Lancet·Rossella Fattori, Tommaso Piva
Apr 23, 2003·Current Opinion in Rheumatology·Dean F Mayer, Sudhir S Kushwaha
May 20, 2003·Immunological Reviews·Douglas R GreenMichael Pinkoski
Oct 8, 2003·Experimental Biology and Medicine·Suwannee UthaisangsookSoichi Haraguchi
Dec 18, 2003·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Ali A HaydarDavid J A Goldsmith
Apr 29, 2004·Transplantation·Phuong-Thu T PhamAlan H Wilkinson
Jun 16, 2005·Current Opinion in Pharmacology·Deborah A Young, Cheryl L Nickerson-Nutter
Jun 28, 2005·Trends in Immunology·Sarah R WalmsleyEdwin R Chilvers
Aug 20, 2005·Nature Reviews. Immunology·Michail Sitkovsky, Dmitriy Lukashev
Feb 14, 2006·Cell·Stephan WullschlegerMichael N Hall
Feb 25, 2006·Human Molecular Genetics·Brinda RavikumarDavid C Rubinsztein
May 16, 2007·The Journal of Biological Chemistry·Stephen C Land, Andrew R Tee
Jul 6, 2007·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Stefan M WeinerLars C Rump
Feb 5, 2008·Pharmacogenomics·Dany AnglicheauEric Thervet
Mar 5, 2008·Seminars in Immunopathology·Dror Luger, Rachel R Caspi
Apr 26, 2008·Investigative Ophthalmology & Visual Science·Lizette M CortesRachel R Caspi
Sep 5, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Andrew M MillerThomas H Reynolds
Apr 25, 2009·Nature Reviews. Immunology·Angus W ThomsonGiorgio Raimondi
Jun 6, 2009·Nature·Erika L PearceYongwon Choi
Jun 23, 2009·Nature·Koichi ArakiRafi Ahmed
Jun 26, 2009·Nature·Kenneth L ScottLynda Chin
Jul 3, 2009·Nature·Martin Prlic, Michael J Bevan
Jul 10, 2009·Nature·David E HarrisonRichard A Miller
Jul 17, 2009·Immunology·Greg M Delgoffe, Jonathan D Powell
Oct 2, 2009·Nature·Lorraine A O' ReillyAndreas Strasser
Jun 12, 2010·Immunological Reviews·Koichi ArakiRafi Ahmed
Jul 16, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ivana R FerrerMandy L Ford
Sep 14, 2010·Current Opinion in Immunology·Christian PeterStephen P Cobbold

❮ Previous
Next ❯

Citations

May 1, 2013·Asia-Pacific Journal of Ophthalmology·Sanjay R Kedhar
Feb 24, 2015·International Reviews of Immunology·Abhisek Bhattacharya, N Tony Eissa
Oct 28, 2015·International Journal of Molecular Sciences·Linlin Wang, Helen Ka Wai Law
Mar 17, 2015·The American Journal of Pathology·Peter J GardnerVirginia L Calder
May 23, 2017·Nature Reviews. Drug Discovery·Lorenzo GalluzziGuido Kroemer
Aug 28, 2020·Scandinavian Journal of Immunology·Bergithe E Oftedal, Anette S B Wolff
Aug 1, 2014·The Journal of Biological Chemistry·Abhisek BhattacharyaN Tony Eissa
Mar 7, 2020·Cell Research·Eva M Pålsson-McDermott, Luke A J O'Neill
Oct 3, 2018·Ocular Immunology and Inflammation·Shasha WangJianhong Zhang
Dec 2, 2020·International Journal of Molecular Sciences·Claudia M Trujillo-VargasCintia S de Paiva

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
flow cytometry
ELISA
confocal microscopy
transgenic

Clinical Trials Mentioned

NCT00908466
NCT00876434

Software Mentioned

CellQuest
GEArray® Expression Analysis Suite

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Related Papers

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Ivana R FerrerMandy L Ford
American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
S Maleki VarekiS M M Haeryfar
Current Opinion in Cell Biology
Koichi ArakiRafi Ahmed
Reviews in Medical Virology
P D Griffiths
© 2021 Meta ULC. All rights reserved