Indian scientists spot ‘Troublemaker’ immune cells driving inflammation

New Delhi: Scientists from CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, have reported a significant finding that could help in the development of new treatments for chronic inflammation. 
Our blood consists of three major types of cells, red blood cells, white blood cells and platelets. White blood cells are the body’s primary immune defence system and help fight off infections by bacteria, viruses and parasites.  The key players are neutrophils that constitute 60–70% of all WBCs. They engulf and clear the pathogen, put out chemicals called cytokines that summon other cells to the site of infection and clear cellular debris once the infectious agent is no longer present.  In their short lifespan of hours to few days, they pack in a lot of action! However, when these cells become overactive or remain in the body for too long, they can cause inflammation, leading to diseases such as fatty liver disease, rheumatoid arthritis, lupus, psoriasis, and even severe cases of COVID-19.
A recent study led by Dr. Sachin Kumar and his team at CSIR-Central Drug Research Institute and published in the prestigious international journal Cell Reports, offers fresh insights into the role of neutrophils. What explains the rogue behaviours of neutrophils in some physiological conditions? Dr Kumar and his team have shown that not all neutrophils are equal. In the mouse model, there is a sub-population of neutrophils that live longer, stay as mature cells longer, and are far more aggressive in causing inflammation. These cells are especially abundant in the liver and tend to appear in both short-term and long-term inflammatory conditions, such as peritonitis (inflammation in the abdominal area) and non-alcoholic steatohepatitis (NASH), a severe liver disease. These neutrophils are characterized by special cell surface markers designated as CD11b+Ly6G+Sca-1+ (hereafter referred to as Sca-1+ neutrophils). 
Dr. Sachin Kumar explained that Sca-1+ neutrophils can produce reactive oxygen species (ROS), toxic enzymes, and form structures called neutrophil extracellular traps to fight off infection like other neutrophils—but sca-1⁺ neutrophils that persist are associated with more tissue damaging behaviours than regular neutrophils.
The researchers used advanced techniques, including high-resolution microscopy and cell sorting, to closely study these cells. They observed that inflammatory signals and metabolic stress (such as poor liver health) can cause regular neutrophils to transform into Sca-1⁺ neutrophils.
Interestingly, these cells were found to store more lipids (fats) inside them, hinting that their activity could be influenced by changes in fat metabolism. This might be why the occurrence of Sca-1+ neutrophils is more common in fatty liver disease.
Even more promising, when the researchers blocked the Sca-1 protein on these cells, the harmful effects—like tissue damage and excess inflammation—were reduced. This suggests that Sca-1 is not just a marker, but may play an active role in driving inflammation.
What makes these findings impactful is that it gives researchers an opportunity to now look for drugs that could specifically target a subpopulation of neutrophils. 
Dr. Radha Rangarajan, Director of CSIR-CDRI, emphasized the value of this finding: “Modulating inflammation is particularly difficult because we lack the tools to specifically stop harmful cellular processes such as neutrophils that continue in a fight-infection mode.  This study opens up the possibility that disabling a specific type of neutrophils could drive down inflammation without affecting the body’s natural defences.”
In humans, Sca-1 like proteins called CD177+ and Ly6E⁺ are expressed on neutrophils. It has been shown that such neutrophils increase during infections and inflammatory diseases. Further research is warranted to evaluate the role of such neutrophil subpopulations in inflammatory conditions. This could pave the way for safer, more targeted treatments for inflammatory and autoimmune diseases.
Study highlights:
  • Scientists from CDRI have identified a novel long-lived, highly inflammatory neutrophil type in mice.
  • They are characterized by the expression of cell surface markers (Sca-1⁺).
  • These neutrophils are predominantly liver-resident and increase during inflammation.
  • Conventional neutrophils can convert to Sca-1⁺ under inflammatory/metabolic stress.
  • Sca-1⁺ neutrophils cause greater tissue damage; pharmacologically targeting these neutrophils alleviates inflammation.
  • Further studies are needed to explore similar subtypes in human neutrophils.

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