Scientists Identify Mechanism for Self-Repair of Thymus, the crucial component of the imamune system

Team of International Researchers Led by Scientists at City of Hope have demonstrated a Way to Boost Thymic Function After Damage in Preculinical Studies. The Team’s Study Results, Published Today in the Journal ImmunityOutline Their Discovery of a Specific Type of Regulatory T Cell That Home Back Into the Thymus and Repair the Organ When It’s Damaged.

Between the lungs and in front of the Heart Sits a Small Gland Called the Thymus That Wields Incredible Power Over Human Health By Producing T Cells, Key Components of Our Immune System. In Cancer Patients, Certain Therapies – Analong With Aging and Stress – Can Deplete T Cell Output, Leaving Individuals Susceptible to Infection and AddiTeal Disease.

“Our Discovery – The Regulatory T Cell Recirculation Back to the Thymus – Promote Repair Through a Process That Hasn’t Been Description Before and Representatives A Novel Pathway to Regeneration In The Gland,” Said Lead Author Andri Lemarquis. “The Findings Open Up A New Translational Angle for Addressing Thymic Fatigue and Damage.

The Role of the Thymus

Over a Lifetime, The Human Body Facs a Wide Variety of Threats from Bacteria, Viruses and Other Dangers, Such As Cancer. T Cells, Made by the Thymus, Fight Pathoges and Malignancies Through Direct Attack or By Teaching Phher Imamune Cells How to Removing Threats.

“BECAUSE there are so many different threats out there, we need an Incredible diversity of these soldiers, or imamune cells, to defend us,” Explained Dr. Lemarquis. “But We Also Need Some Kind of Control, So We Don’t get Get a Civil War In Our Body, Like An Autoimmune Disease. This Requires A School to Teach These Cells to Protect Us and That School is the Thymus.”

UNFORTUNATELY, THE THYMUS IS HIGHLY SUSCEPTIBLE TO INJury Caused by Stress, Infections, Aging and Cancer Therapies.

“If you fear Cancer Therapies, Your Thymus is Going to Shrink,” Said Dr. Lemarquis. “Without Some Help To Grow Again, Patients Won’t Get What’s Called Immune Reconstitution, In Which New Protective T Cells Are Produced. OUR WORK IS TRYING TO BOOST THE THYMUS WHYMUS WHIS BASIC PROTECTION.”

Finding the Key to Regeneration

Dr. Lemarquis and the Research Team Set Out to Explore Mechanisms of Thymus Regeneration in Two Settings, Cancer Therapies and Aging, Which Go Together Since Aging Cancer Patients Are Highly Susceptible to Infection. The Scientists First Studied Treatment-Relanted Injuries in Murine Models to Understand How the Thymus is Damaged and Under What Conditions It Begins To Rebound. Then, They Combined Imaging and Analyzing Techniques with Machine Learning to Identify Specific Pathways That Are Active During Regeneration.

What They Found was a novel and Prevously UndesCricBed Population of Thymic Regulatory T Cells (TRAGS) That Accumulate in the Thymus After Injury and Secret A Growth Factor Called Amphiregulin. Dr. Lemarquis and His Collaborators Were Able To Show That Who These Tregs Were Added to the Bloodstream Intravenly, They Found Their Way Back to the Thymus Where Amphiregulin then Helped Teach the Thymus to Regenerate and Develope More T Cells. Next, They TestD Their Findings in Human Tissue Samples and Saw the Same Results.

“We Were Able To Go from Mechanismic Insights in Mice to Seeing That the Same Pathways Were Operating in the Human Setting,” Said Dr. Lemarquis.

“There are a lot of adoptive Cell therapies round now in the Tregs Space, so that opens up the possibility for a translational approach where this subset of TRAGS can be used to regenerate tissues, and specifically in the thymus and the immeli system.”

He Said the Researchers Were Also Surprised to Find That the Results Extended to Older Mice, Too, The Was Believe That Lost Thymic Function From Aging May Not Be Treatable.

“There are recent Studies That Show That If You Lose Thymic Function in Aging, You Will Have an Increeed Rate of Mortality Due to Higher Rate of Cancers, Infections and Autoimmunity,” Said Dr. Lemarquis.

“And What We Could Show Was That We We Transferred Tregs Into Mice Receue Cancepies, We Could Even Boost Their Function. It’s not Only the Young Thymus That Receptive To these Signals to Regenerate, But Even The Thymus In Olider Patients Receiving Cancer Therapies. “

From Lab to Life

The Work Outlined in the Immunity Paper Builds on a Research Program Established in the Late 1990s by Dr. Van den BRink to Boost Imamune Reconstitution in Patients Receue Cancer Therapies, Special in the Bone Marrow Transplantation Field.

“He Laid the Groundwork Over Decades That Proceeds Us With the Models, Tools and Data To Get To Ware We Are Today,” Said Dr. Lemarquis. “There’s Also Been Tremendous Work on Regulatory T Cells, and We Brought Together These Two Fields to See if’s Something Therapeutic That We Can from the Seting of Thymic Injury. But Brillian Minds Before US Led The Way.”

Next, The Researchers are delving into a wide atlas of human thymic samples from cancer patients of different ages who have either thymic rebound or are in the degenerative phase to understand more how to bechways might intertwine with the regulatory t cells to Further Improve Funte Tion. They are also Looking for Other Ways to Apply Their Findings in a Human Setting, For Example, by Potentially Using Synthetic Biology To Modify T Cells to Overproduce Amphiregulin or other Beneficial Factors.

“We have a Thymic Research Program Now at City of Hope, with Computational Biologists and Postdoctoral Scholars who are Working on Different Projects, Along With Collaborators in the Clinic Who Can Help Move Or Findings Forward,” Said Dr. Lemarquis. “I Think There is Great Potential for Tregs and Amphiregulin to Be Used Therapeutically in Patients Receue Cancer Therapies to Ameliorate Imamune Function.”

In Addition to City of Hope Scientists, The Paper “Recirculating Regulatory T Cells Mediate Thymic Regeneration Through Following Thymic Damage” Included Authors from Memorial Sloan Kettering Cancer Center, The University of Gothenburg In Sweden, Bambino Gesù Children’s In Rome, New York- Presbyterian Morgan Stanley Children’s Hospital, The University of Washington, Fred Hutchinson Cancer In Seattle and Weill Cornell Medical College in New York.