Biochemical controls: over natural killer cells (Introduction)

by David Turell , Monday, August 12, 2024, 18:31 (101 days ago) @ David Turell

Several agent proteins found:

https://www.the-scientist.com/maintaining-nk-cells-killer-instincts-72062

"...a 2017 study showed that tumors can avoid being killed by triggering the release of transforming growth factor beta (TGFb), a molecule that can turn NK cells into intermediate type 1 innate lymphoid cells (intILC1).1 This immune cell type is much less effective against tumors, which can undermine immunotherapy efforts.

“'Tumors have developed these fantastic environments to survive,” said Sebastian Scheer, an immunologist at the Luxembourg Institute of Health and coauthor of the study. But that environment is not the only way for NK cells to transform into intILC1. In a new study in Cell Reports, a team at Monash University led by Scheer found that the molecule disruptor of telomeric silencing 1-like histone lysine methyltransferase (DOT1L) plays an important role in maintaining NK cell functions.2 When DOT1L levels decline, the NK cells turn into benign intILC1 even in the absence of cancer-induced TGFb.

"Changing a cell’s functions so drastically often requires changing its genetic programming, so the team investigated DOT1L, an epigenetic modifier that changes cells’ epigenetic marks. DOT1L seemed to shape the unique way that NK cells read their genome.

"When the researchers deleted DOT1L from mature NK cells in the new study, it became clear that deleting just this one protein was enough to change the levels of genes and proteins expressed in the cell, including those of a transcription factor called myocyte enhancer factor 2C (MEF2C) that was previously linked to NK cell function.3 As a result, some of the NK cells turned into intILC1, despite not being near tumors or exposed to TGFb.

***

"Eric Vivier, an immunologist at Aix-Marseille University who was not involved in the study, said this work fills in some of the gaps in scientists’ understanding of how NK cells might turn into intILC1. However, he suspects DOT1L is not the only protein in play. “It would be very surprising if DOT1L by itself is both necessary and sufficient for this transition,” he said. “There will be many more mechanisms to dissect.'”

Comment: it is amazing to me that such specific proteins create specific functions as the intent of their biochemical reactions. Only design can do this.