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A fantastic showdown between the short version of sfTSLP and the long version of TSLP: How do they change the immune response?
In the world of immunology, Thymic stromal lymphopoietin (TSLP) is rapidly becoming an important focus of research. As a cytokine, TSLP plays a crucial role in multiple physiological and pathological processes of the immune system. This article will delve into the relationship between the short version of sfTSLP and the long version of TSLP and reveal how they influence each other's immune response.
With a preliminary understanding of TSLP, we know that it comes from the stromal cells of the thymus and was originally found to be a growth factor that promotes the survival and proliferation of B lymphocytes. The TSLP gene can produce two different transcript variants: long version TSLP (lfTSLP) and short version TSLP (sfTSLP). The amino acid compositions of these two variants are 159 and 63, respectively. Although they share the same carboxyl terminus, their physiological functions are completely different.
TSLP plays a key role in the proliferation and development of immune cells, but its short variant sfTSLP plays the exact opposite role.
Function and role of sfTSLP
The expression of sfTSLP is sustained in normal human bronchial epithelial cells and other similar cells, and does not increase significantly due to inflammation. This variant exhibits strong protective effects, such as the ability to prevent airway epithelial barrier damage caused by large dust mite antigens, and has shown potential in an asthma-like model in mice. In addition, sfTSLP can also alleviate colitis caused by sodium dextrosulfonate, showing its importance in the intestinal inflammatory process.
Immune response to long version of TSLP
Compared to sfTSLP, the long version of TSLP plays a more active role in stimulating immune responses. TSLP is released after epithelial cell injury or infection and is up-regulated through stimulation such as Toll-like receptors (TLRs). This release behavior activates dendritic cells (DCs) and promotes the differentiation of immature CD4+ T cells into TH2-type cells, thereby releasing pro-inflammatory cytokines. This reaction is closely related to immune diseases such as allergies and asthma.
The release of TSLP can be regarded as an "alarm", telling the immune system to activate defense mechanisms against potentially harmful substances.
The wonderful balance of the immune system
Although the functions and effects of the two are completely different, they have a synergistic effect in maintaining the balance of the immune system. The anti-inflammatory properties of sfTSLP may help suppress excessive inflammatory responses, while TSLP orchestrates necessary responses to fight pathogens. In some disease conditions, such as allergic diseases and autoimmune diseases, the balance between the two may be disrupted, leading to worsening of the condition.
Looking to the future, the TSLP signaling pathway has become a new target for treatment. For example, Amgen's Tezepelumab has been approved for the treatment of severe asthma. In addition, inhibitors and related therapeutic strategies targeting these pathways are under active development.
How to balance the effects of sfTSLP and long-form TSLP may become the key to future research, and is expected to open new doors for new treatments for allergic and autoimmune diseases.
Conclusion
The subtle confrontation between the short version of sfTSLP and the long version of TSLP not only advances our understanding of immune system function, but may also provide new perspectives for future treatment options. In this fantastic showdown of immune responses, how will scientists uncover deeper truths to treat currently intractable diseases?
