Transcript Autoimmune Diseases

PHM142 Fall 2016
Coordinator: Dr. Jeffrey Henderson
Instructor: Dr. David Hampson
AUTOIMMUNE DISEASE AND
MICRORNAS
Farhat Hossain, Baldeep Litt and
Sheldon Keith Pereira
AUTOIMMUNE DISEASES
Caused by immune system initiating an attack on self-molecules
Due to genetic or environmental factors (diet, where you live)
PAGE, L. M., DU TOIT, D. F., & PAGE, B. J. (N.D.)
HTTP://MISSINGLINK.UCSF.EDU/LM/IMMUNOLOGY_MODULE/PROLOGUE/OBJECTIVES/OBJ02.HTML
EXAMPLES
Rheumatoid arthritis
Multiple Sclerosis
Type 1 Diabetes
Vitiligo
Systemic lupus erythematosus
PAGE, L. M., DU TOIT, D. F., & PAGE, B. J. (N.D.)
MIRNA SYNTHESIS
MiRNAs are non coding regulatory RNAs that repress targeted gene expression by
affecting mRNA
MiRNAs act via two main main mechanism to directly interfere with mRNA translation
or degrade targeted mRNAs.
QU ET AL. 2014, DENG ET AL., 2014
HUSAKOVA, 2016
CONTRIBUTION OF MIRNAS IN SLE
miRNA 146a
• Negatively
regulates Type I
IFN pathway
• Low expression
associated with
onset of SLE
miRNA 125a
miRNA 126 and
148 a
• Negatively
regulates RANTES
(inflammatory
cytokine
• Low expression
associated with
renal inflammation
in SLE
• High expression
Inhibits translation
of DNMT1
• Decreased activity
of DNMT
associated with
SLE disease onset
Husakova, 2016; Kiefer et al.,2012; Deng et al., 2014)
CERIBELLI ET AL., 2011
CERIBELLI ET AL., 2011
SUMMARY
Autoimmune disorders are caused by the immune system attacking healthy cells in the
body
Examples of rheumatoid arthritis, multiple sclerosis, type 1diabetes, vitiligo and
systemic lupus erythematosus
MiRNA’s are able to repress targeted gene expression by interfering with translation
of mRNA or degradation of mRNA
In SLE, low expression of MiRNA 125a and MiRNA 146a cause renal inflammation
and production of autoantibodies respectively. High expression of MiR 126 and 148a
causes decreased activity of DNMT1
miRNAs cause autoimmune diseases by two major pathways: downregulation of
miRNAs that directly regulate pro-inflammatory cytokines and upregulation of
miRNAs that repress DNA methyltransferases whose function are used to regulate
auto-immune related genes.
REFERENCES
Ceribelli, A., Yao, B., Dominguez‐Gutierrez, P. R., & Chan, E. K. (2011). Lupus T cells switched on by DNA
hypomethylation via microRNA?. Arthritis & Rheumatism, 63(5), 1177-1181.
Ceribelli, A., Yao, B., Dominguez-Gutierrez, P. R., Nahid, M. A., Satoh, M., & Chan, E. K. (2011). MicroRNAs in
systemic rheumatic diseases. Arthritis research & therapy, 13(4), 1.
Kiefer, K., Oropallo, M. A., Cancro, M. P., & Marshak-Rothstein, A. (2012). Role of type I interferons in the
activation of autoreactive B cells. Immunology and cell biology, 90(5), 498-504.
Deng, X., Su, Y., Wu, H., Wu, R., Zhang, P., Dai, Y., ... & Lu, Q. (2015). The role of microRNAs in autoimmune
diseases with skin involvement. Scandinavian journal of immunology, 81(3), 153-165.
Husakova, M. (2016). MicroRNAs in the key events of systemic lupus erythematosus pathogenesis.
Page, L. M., du Toit, D. F., & Page, B. J. (n.d.). Understanding Autoimmune Disease - a review article for the
layman. Retrieved from
http://www.sun.ac.za/english/faculty/healthsciences/biomedical_sciences/Documents/Anatomy%20and%20Hi
stology/Understanding%20Autoimmune%20Disease.pdf
Saito, Y., Saito, H., Liang, G., & Friedman, J. M. (2014). Epigenetic alterations and microRNA misexpression in
cancer and autoimmune diseases: a critical review. Clinical reviews in allergy & immunology, 47(2), 128-135.
Qu, Z., Li, W., & Fu, B. (2014). MicroRNAs in autoimmune diseases. BioMed research international, 2014.
Ying, S. Y., Chang, D. C., & Lin, S. L. (2008). The microRNA (miRNA): overview of the RNA genes that modulate
gene function. Molecular biotechnology, 38(3), 257-268.