Soldiers of our body starve to fight enemies, says study

The regulatory T-cells (Tregs), which are responsible for suppressing aberrant immune responses that attack our body’s healthy cells and tissues and act as guards, face harsh conditions like starvation. For survival and continued function, these cells resort to autophagy (cannibalism) that can recycle non-essential portions of a starving cell to generate energy, says a study.

Scientists from the National Centre for Biological Sciences (NCBS), Bengaluru, and the Institute for Stem Cell Biology and Regenerative Medicine (inStem), have explained in international journal `eLife’ as to how the defence mechanism in our body works.

Thymus, an important gland producing several hormones is also where key cells of our immune system, T-cells, mature and divide rapidly to put up a defence. This must, however, shut down soon after the infection is curbed, which is achieved by Tregs.

These findings are part of the research by Prof Apurva Sarin and Prof Nimi Marcel, scientists from NCBS and inStem. The same is published in ‘eLife’ edited by Nobel Prize-winning cell biologist Randy Schekman and supported by Wellcome Trust. “In a lab dish, a collection of Tregs are being starved. In six hours, autophagy (auto-‘self ‘, phagos – ‘eating’) sets in and the cells begin to cannibalize to stay alive,” NCBS research communications officer Anusha Krishnan told TOI.

During their research, the duo has identified that a well-known signalling molecule–primarily involved in development–to be essential for autophagy. They have demonstrated that Tregs need the protein Notch-1 to trigger autophagy at just the right time to survive starvation and carry out their policing duties.

Notch-1 is a receptor and an important part of the Notch-signalling pathway involved in the development of T-cells. Notch-signalling also plays a role in formation of nerve cells, blood vessels, and the pancreas.Faulty notch-signalling is implicated in many cancers and multiple sclerosis.

“Until now, most work on Notch-1 focussed on how it regulates a cell’s fate, what a cell will develop into. The unique part of our study is that we describe its post-developmental role in mature cells,” Marcel said.

Using mice, the duo investigated Notch-1 mediated signalling in mature and starving Tregs. When Tregs isolated from mice are grown and deprived of nutrition, Notch-1 is needed to trigger autophagy. Tregs die in the absence of this signalling.

“We’ve also establish the connection between autophagy and Notch-1 signalling. Both are very old, evolutionarily conserved pathways, and this is the first time a link has been found between the two,” Marcel added.