NOD2 acts as a master regulator of regeneration pathways in the thymus

Description:

NOD2 Mediated Thymic Regeneration Boosts Compromised Immune Function

 

Promotion of thymic regeneration through reduction or inhibition of nucleotide-binding oligomerization domain-containing protein 2 (NOD2) by upregulating regenerative molecules (e.g., interleukin (IL)-22, IL-23, and bone morphogenetic protein 4 (BMP4)).

 

 

As the primary site for T cell development, thymic regeneration is critical for the renewal and development of immune competence following stress (e.g., conditioning required for hematopoietic stem cell transplant or cytotoxic cancer treatments). IL-22 and BMP4 secretion through innate lymphoid (ILCs)- and endothelial (ECs)- cellular activity have been established as important for thymic regeneration. However, the pathways that trigger these mechanisms are poorly understood. Dr. Dudakov established how NOD2 governs these pathways and that mice deficient in NOD2 show increased intrathymic levels of IL-22, IL-23, and BMP4. By targeting NOD2 expression, thymus regeneration could be induced in patients whose thymus has been damaged by age, infection, and cancer therapies (e.g., chemotherapy and irradiation).

 

 

<ul>

       <li>Age-related immune decline</li>

       <li>Infection</li>

       <li>Cancer therapies (e.g., chemotherapy and irradiation)</li>

</ul>

       

 

<ul>

       <li>Promotes thymic regeneration </li>

       <li>Selective mechanism of action conferred through cell-specificity</li> 

</ul>

 

The global tissue regeneration market is predicted to reach USD 109 billion by 2024. With a CAGR of 34.5%, this is a strong predicted growth period driven by wound healing applications and the growing range of aged people, as well as technological advancements, and adoption of immunotherapy. This market includes cell therapy, tissue engineering, chemically induced and therapeutic cloning, as well we technologies used to harness or stimulate the body’s innate healing ability. In the US alone, approximately 650,000 cancer patients will undergo chemotherapy per year. According to the Centers for Disease Control, cancer patients treated with chemotherapy are more likely to get infections. In 2018, 60,000 patients were admitted to hospital due to compromised immune response, 14 of which were fatal.

 

<ul>

       <li> Jarrod Dudakov, PhD - Clinical Research Division</li>

</ul>

 

Preclinical <em>in vivo</em>

 

Patent pending

 

18086Dudakov_NOD2.pdf

 

NOD2 | thymus | regeneration |

 

NOD2-Mediated-Thymic-Regeneration-18-086

 

 

 

Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Ziyan Zhang
Technology Manager
Fred Hutchinson Cancer Research Center
zzhang3@fredhutch.org
Inventors:
Jarrod Dudakov
Sinéad Kinsella
Keywords:
Target
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