B-Cell Immune Checkpoint - TIM-1

Creative Biolabs, a pioneering leader in antibody development and immune checkpoint research, presents an in-depth exploration of TIM-1 as an emerging immune checkpoint in the context of B-cell immune regulation. With a steadfast commitment to unraveling the complexities of the immune system, we are dedicated to advancing scientific knowledge and therapeutic strategies for immune checkpoints.

Brief Overview of TIM-1

TIM-1, short for T-cell immunoglobulin and mucin domain 1, initially gained prominence as a T-cell surface receptor. However, recent investigations have revealed its versatile presence and function in various immune cell populations, including B cells. As a type I transmembrane glycoprotein, TIM-1 exerts diverse effects on immune responses, influencing both immune activation and tolerance.

Fig. 1 Tim-1, a phosphatidylserine receptor expressed on B cells. (Xiao S, et al., 2020)

In the context of B-cell immunity, TIM-1 holds significant promise as a regulator of B-cell activation, differentiation, and antibody production. By unraveling the intricate mechanisms underlying TIM-1-mediated signaling pathways, researchers aim to unlock novel therapeutic avenues for immune-related diseases.

TIM-1 Structure and Expression

The structure of TIM-1 exhibits distinct domains that contribute to its diverse functions.

• TIM-1 consists of an extracellular region comprising an immunoglobulin variable (IgV) domain, a mucin-like domain, and an intracellular region with conserved signaling motifs. This unique composition endows TIM-1 with the ability to engage in various interactions with ligands and co-receptors, modulating immune responses in a context-dependent manner.
• The expression of TIM-1 extends beyond T cells and encompasses multiple immune cell subsets, including B cells. Understanding the precise spatiotemporal expression patterns of TIM-1 in B-cell populations is crucial for unraveling its functional implications and therapeutic potential.

Upon engagement with its ligands, TIM-1 initiates a cascade of intracellular signaling events, culminating in the modulation of B-cell responses. The activation of TIM-1 has been shown to

• Enhance B-cell receptor (BCR) signaling, promoting B-cell activation, survival, and antibody production.
• Potentiate co-stimulatory signals, thereby augmenting the interaction between B cells and T follicular helper (Tfh) cells.

TIM-1 and B-Cell-Associated Diseases

Emerging evidence suggests that dysregulation of TIM-1 signaling in B-cell immunity is implicated in the pathogenesis of various diseases.

• Aberrant TIM-1 expression has been associated with the development of autoimmune disorders, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
• Conversely, the upregulation of TIM-1 on B cells has been observed in certain B-cell malignancies, such as B-cell lymphomas and chronic lymphocytic leukemia (CLL).

These findings highlight the intricate role of TIM-1 in disease progression and provide a basis for exploring TIM-1 as a potential therapeutic target in these conditions.

Therapeutics of Targeting TIM-1

The emergence of immune checkpoint blockade therapies, particularly those targeting PD-1 and CTLA-4, has revolutionized cancer treatment. These breakthroughs have underscored the potential of immune checkpoints as druggable targets. Given its emerging significance in B-cell immunity, TIM-1 represents a compelling candidate for therapeutic intervention.

Manipulating TIM-1 signaling pathways through monoclonal antibodies, antibody-drug conjugates (ADCs), or other innovative strategies holds promise in modulating B-cell responses for therapeutic benefit. Preclinical and clinical investigations are warranted to further explore the therapeutic potential of targeting TIM-1 in various disease contexts.

As the field of immune checkpoint research continues to evolve, the discovery of novel checkpoints such as TIM-1 expands our understanding of immune regulation and provides fresh avenues for therapeutic interventions. Creative Biolabs remains at the forefront of pioneering research, diligently striving to uncover the complexities of immune checkpoints and their implications in disease pathogenesis.

References

1. Xiao S, et al. Checkpoint receptor TIGIT expressed on Tim-1+ B cells regulates tissue inflammation. Cell reports, 2020, 32(2): 107892.
2. Yeung M Y, et al. TIM-1 signaling is required for maintenance and induction of regulatory B cells. American Journal of Transplantation, 2015, 15(4): 942-953.

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