Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Alternative RNA Splicing02:18

Alternative RNA Splicing

24.6K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
24.6K
RNA Splicing01:32

RNA Splicing

60.3K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.3K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

14.6K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
14.6K
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

3.9K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.9K
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

15.9K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
15.9K
Exon Recombination02:32

Exon Recombination

4.1K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon...
4.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Development of a Humanized Anti-Fibrotic Antibody Targeting Extracellular Collagen Assembly to Reduce Post-Traumatic Scarring.

bioRxiv : the preprint server for biology·2026
Same author

Higher order receptor clustering due to the IgG3 subclass is necessary for TLR4 signaling and tolerance induction by novel human anti-TLR4 antibodies.

mAbs·2025
Same author

Protective Efficacy of Novel Engineered Human ACE2-Fc Fusion Protein Against Pan-SARS-CoV-2 Infection In Vitro and in Vivo.

Journal of medicinal chemistry·2023
Same author

Applying Artificial Intelligence to Identify Common Targets for Treatment of Asthma, Eczema, and Food Allergy.

International archives of allergy and immunology·2023
Same author

Antiaging Vaccines Targeting Senescent Cells.

Rejuvenation research·2022
Same author

Stem Cell Rejuvenation by Restoration of Youthful Metabolic Compartmentalization.

Rejuvenation research·2021

Related Experiment Video

Updated: Jan 12, 2026

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

13.3K

Alternate splicing converts human CD137 from costimulatory to immunosuppressive function.

Manuel Rojas1, Luke S Heuer2, Weici Zhang2

  • 1Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States; Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.

Journal of Autoimmunity
|November 8, 2025
PubMed
Summary

Soluble CD137 (sCD137) splice variants, unlike their membrane-bound counterparts, exhibit immunosuppressive properties. These novel sCD137 variants show potential as a new therapeutic strategy for treating inflammatory and autoimmune diseases.

Keywords:
4-1BB4-1BBLAutoimmunityCD137CD137LSoluble CD137Tnfrsf9Tnfsf9ToleranceTregs

More Related Videos

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

15.4K
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

9.3K

Related Experiment Videos

Last Updated: Jan 12, 2026

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

13.3K
Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

15.4K
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

9.3K

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Membrane-bound CD137 (mCD137) is a known costimulatory molecule.
  • Alternative splicing generates soluble CD137 (sCD137) transcripts with unknown functions.

Purpose of the Study:

  • To investigate the structure, function, and therapeutic potential of human sCD137 splice variants.
  • To compare the properties of sCD137 with mCD137.

Main Methods:

  • Characterization of sCD137 isoform structure.
  • Analysis of sCD137 expression in activated human regulatory T cells (Tregs).
  • Engineering of recombinant Fc-Hu-sCD137 variants and assessment of their effects on T cell function.
  • Evaluation of the mTOR pathway involvement.

Main Results:

  • sCD137 isoforms lack the CRD4 region and possess unique structures.
  • Activated human Tregs express both sCD137 isoforms, identifying a specific Treg phenotype.
  • Engineered sCD137 variants demonstrated immunosuppressive activity, inhibiting T cell proliferation and IFN-γ secretion.
  • sCD137-mediated immunosuppression involves downregulation of the mTORC1 pathway (S6 and 4EBP1).

Conclusions:

  • Human sCD137 variants are immunosuppressive, contrasting with the costimulatory mCD137.
  • sCD137 variants represent a potential novel therapeutic target for inflammatory and autoimmune conditions.