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Peer-Reviewed Publication
J Clin Invest2026;136(15)August 3, 2026Journal Article

TRAIL splice variant TRAILshort disrupts T cell receptor signaling and promotes immune tolerance in vivo.

Shahrzad Jalali1, Sekar Natesampillai1, Zilin Nie1, Ying Zhang1, Ismail Can2, Aswath P Chandrasekar1,3, Brianna M Hameister1, Cristina Correia4, Tuantuan V Zhao5, Dong-Gi Mun3, Enrique Garcia-Rivera6, Robert Matson7, Ashton Krogman1, Mark A Maynes1, Robin Batchelor1, Dileep D Monie4,8, Hu Li4, Atta Behfar9, Saad S Kenderian2,10, Akhilesh Pandey3,11,12, Stephen M Ansell2, Timucin Taner13,14, Cornelia Weyand3, Daniel D Billadeau13, Andrew D Badley1,10
1Division of Infectious Diseases.
2Division of Hematology.
3Department of Laboratory Medicine and Pathology, and.
4Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
5Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.
6Formation Bio, New York, New York, USA.
7nference Inc., Cambridge, Massachusetts, USA.
8Department of Neurological Surgery, Albert Einstein College of Medicine-Montefiore Medical Center, Bronx, New York, USA.
9Department of Cardiovascular Medicine.
10Department of Molecular Medicine, and.
11Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
12Manipal Academy of Higher Education, Manipal, Karnataka, India.
13Department of Immunology, and.
14Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
PubMed DOI

Abstract

TRAIL is a TNF family ligand that trimerizes TRAIL-R1 (DR4) or TRAIL-R2 (DR5) to induce apoptosis, necroptosis, and/or NF-κB activation in receptor-bearing cells. We previously identified TRAILshort as a splice variant of TRAIL that lacks cysteine 230, cannot trimerize, and acts as a dominant-negative ligand that blocks TRAIL-mediated apoptosis. TRAILshort is expressed on cell surfaces and within…

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