Immunity: Key insights into the complex biology of tissue-specific T cells

Recent pressure to maximize vaccine efficacy has stirred up many new discoveries in the field of immunology, revealing many paradigms of untapped therapeutic potential
.
Tissue-resident memory T cells (T_RM cells), an immune cell that provides long-lasting protection against pathogens attacking specific organs and tissues
.

In a new study published December 28, 2022, scientists at the UC San Diego School of Medicine have revealed cell biology in the T_RM gut, which could inspire a new generation of precise treatments
for infections, cancer, and autoimmune diseases.

After experiencing an infection, the immune system leaves memory T cells that maintain a long-term molecular memory of the pathogen and are ready to sound the alarm if the
pathogen reappears.
While some memory T cells are designed to circulate through the bloodstream and provide whole-body protection, others reside in specific organs specifically designed to fight pathogens
that target that part of the body.
These_TRM cells can provide lifelong immunity to the target tissue, but can also promote autoimmune diseases if coped
.

"T_RM cells are the first responders, right on the front lines of infection," said
senior author John T.
Chang, M.
D.
, a professor at the University of California, San Diego School of Medicine.
"Most of our vaccines are designed to provide systemic immunity, but if we focus on enhancing tissue-specific cells that encounter pathogens first, we may get better protection
.
"

For example, the best way to fight respiratory viruses may be to strengthen the cells in the nose and lungs of the T-virus RM, as well as a pathogenic gut microbe, preferably by strengthening the cells
in the T _RM gut.
Therefore, we aim to develop treatments that promote the formation and maintenance of T_RM cells or, in the case of autoimmune diseases, remove immune cells
by disrupting these same pathways.

The problem is that scientists still have a lot to learn about what helps_Trm cells form and survive, and these rules can be quite different
in each tissue type.

To explore this, the researchers conducted a series of experiments to characterize cells in T_RM mice from four different regions of the gut: two organs (small intestine and colon), each with two different tissue layers (inner epithelial and proprium).

Experiments have shown that cells of T_RM per tissue type exhibit different cytokine and granzyme expression patterns, as well as substantial transcriptional, epigenetic, and functional heterogeneity
.
In other words, in each part of the gut, the same type of immune cells appear to differ
greatly in molecular composition, function, and the chemical signals they rely on.

Further reinforcing this, each cell population also exhibits a different dependence on demesoembryonic proteins (Eomes), a transcription factor known to influence the development of
T_RM cells.
Eomes are often thought to inhibit T_RM These cells are based on data previously collected from the skin, liver and kidneys, but new experiments show that the opposite is true in the small intestine
.
There, Eomes was shown in T_RM cells
.
However, this is not the case in the colon, which highlights the high degree of environmental specificity
even in the intestine.

Future studies will continue to define the rules for the formation and maintenance of T_RM cells in other tissues and explore what drives their specificity
.
For example, the authors suggest that differences in the microbiota of the small intestine and colon may contribute to their unique demand for T_RM cells, so manipulating the microbiome may be another way
to modulate gut immune cells.

"In the future, we hope to consider vaccines and other treatments tailored to the specific needs of each organ," Chang said
.
"By understanding what each tissue type needs to support the formation and maintenance of T_RM cells, we can provide the most effective immune defense against disease
.
"