Description:
MAIT Cell Immunomodulation for Targeted Treatment of Inflammatory Diseases
MAIT cells undergo targeted therapeutic exploitation to alter CTLA-4 expression and dampen inflammatory responses.
Mucosal-associated invariant T (MAIT) cells are non-conventional T cells that localize within inflamed tissue. Upon activation, MAIT cells act as effector cells with both cytotoxic and pro-inflammatory properties. The Prlic Lab determined MAIT cells have a unique transcriptional signature based on whether located within the blood or inflamed tissue. Conventional T cells activate through a TCR signal, however, MAIT cells require both TCR and inflammatory signals to elicit sustained effector function. They also established that an inflammatory signal could elicit CTLA-4 expression ex vivo, and that use of both TCR and inflammatory signals had a synergistic effect. Given MAIT cells detect bacteria-derived metabolites and not peptides, MAIT cells can be specifically targeted to alter CTLA-4 expression for immunomodulatory purposes.
<ul>
<li>Graft-vs-host disease</li>
<li>Post-transplantation immune reconstitution</li>
<li>Tumor treatment</li>
<li>Mucosal inflammatory diseases (e.g., Crohn’s disease)</li>
</ul>
<ul>
<li>Controlled expression of CLTA-4 in MAIT cells</li>
<li>Targeted immunomodulation within inflamed mucosal tissues</li>
<li>MAIT cell activation will not affect conventional T cell activity</li>
</ul>
In 2015, the World Health Organization estimated that 3 million US adults (1.3% of the population) were diagnosed with either Crohn’s disease or ulcerative colitis. The global anti-inflammatory therapeutics market is predicted to reach USD 130.6 billion by 2026 with a predicted CAGR of 8.5% between 2018 and 2026. The combination of increasing prevalence of inflammatory diseases (e.g., Crohn’s) and an impressive drug pipeline are boosting the market growth.
<ul>
<li>Martin Prlic, PhD - Vaccine and Infectious Disease Division </li>
</ul>
Preclinical <em>in vitro</em>
Patent pending
17-068PrlicMAIT.pdf
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MAIT-Immunomodulation-Treatment-Inflammatory-Disease-17-068