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Researchers say they have discovered how regulatory T cells (Tregs) remain intact and functional during activation.
The team found that once Tregs are activated, they are protected by autophagy, which maintains metabolic balance.
Hongbo Chi, PhD, of St. Jude Children’s Hospital in Memphis, Tennessee, and his colleagues described this discovery in Nature Immunology.
Until this study, no one knew how Tregs maintained themselves when activated.
“Regulatory T cells are very specialized cells that require activation to perform their function in curtailing undesirable immune responses,” Dr Chi explained. “But this activation is a double-edged sword, in that this very activation can destabilize them. They need to modulate this activation, or they will lose their stability and many of them will die. That could damage immune function.”
Dr Chi and his colleagues performed imaging studies in activated Tregs and found that autophagy was functional in the cells.
In experiments with mice, the researchers deleted Atg7 or Atg5, genes whose functions are necessary for autophagy in Tregs.
The mice showed key characteristics of Treg malfunction, including inflammatory and autoimmune disorders. The mice also more readily cleared tumors from their bodies, due to activated immune systems.
Dr Chi said that eliminating autophagy also affected the fate of Tregs.
“Once those T cells lack autophagy activity, they tend to undergo excessive cell death,” he said. “But even for the remaining surviving cells, they tend to be overly activated and lose their identity because they start to behave like non-regulatory T cells. That is why loss of autophagy in regulatory T cells produces a 2-fold effect on both survival and stability.”
Detailed analysis also revealed how the elimination of autophagy affected the basic energy-producing metabolic pathways of Tregs, compromising their function.
Dr Chi said this new understanding of autophagy’s role in Tregs could enable a 2-fold approach to immune therapy for cancers. Namely, by strengthening tumor-associated immune responses, targeting Treg autophagy could act in synergy with strategies that block autophagy in tumor cells.
In this study, the researchers used a transplanted colon cancer cell line. In further studies, they plan to explore the role of autophagy in immune reactions toward other tumor cell types to determine whether such therapies might be effective in a broad range of cancers.
The team also hopes to gain a better understanding of the detailed biochemical mechanisms regulating how autophagy connects to the cell’s metabolic pathways. 
Image by Kathryn Iacono
Researchers say they have discovered how regulatory T cells (Tregs) remain intact and functional during activation.
The team found that once Tregs are activated, they are protected by autophagy, which maintains metabolic balance.
Hongbo Chi, PhD, of St. Jude Children’s Hospital in Memphis, Tennessee, and his colleagues described this discovery in Nature Immunology.
Until this study, no one knew how Tregs maintained themselves when activated.
“Regulatory T cells are very specialized cells that require activation to perform their function in curtailing undesirable immune responses,” Dr Chi explained. “But this activation is a double-edged sword, in that this very activation can destabilize them. They need to modulate this activation, or they will lose their stability and many of them will die. That could damage immune function.”
Dr Chi and his colleagues performed imaging studies in activated Tregs and found that autophagy was functional in the cells.
In experiments with mice, the researchers deleted Atg7 or Atg5, genes whose functions are necessary for autophagy in Tregs.
The mice showed key characteristics of Treg malfunction, including inflammatory and autoimmune disorders. The mice also more readily cleared tumors from their bodies, due to activated immune systems.
Dr Chi said that eliminating autophagy also affected the fate of Tregs.
“Once those T cells lack autophagy activity, they tend to undergo excessive cell death,” he said. “But even for the remaining surviving cells, they tend to be overly activated and lose their identity because they start to behave like non-regulatory T cells. That is why loss of autophagy in regulatory T cells produces a 2-fold effect on both survival and stability.”
Detailed analysis also revealed how the elimination of autophagy affected the basic energy-producing metabolic pathways of Tregs, compromising their function.
Dr Chi said this new understanding of autophagy’s role in Tregs could enable a 2-fold approach to immune therapy for cancers. Namely, by strengthening tumor-associated immune responses, targeting Treg autophagy could act in synergy with strategies that block autophagy in tumor cells.
In this study, the researchers used a transplanted colon cancer cell line. In further studies, they plan to explore the role of autophagy in immune reactions toward other tumor cell types to determine whether such therapies might be effective in a broad range of cancers.
The team also hopes to gain a better understanding of the detailed biochemical mechanisms regulating how autophagy connects to the cell’s metabolic pathways.
Image by Kathryn Iacono
Researchers say they have discovered how regulatory T cells (Tregs) remain intact and functional during activation.
The team found that once Tregs are activated, they are protected by autophagy, which maintains metabolic balance.
Hongbo Chi, PhD, of St. Jude Children’s Hospital in Memphis, Tennessee, and his colleagues described this discovery in Nature Immunology.
Until this study, no one knew how Tregs maintained themselves when activated.
“Regulatory T cells are very specialized cells that require activation to perform their function in curtailing undesirable immune responses,” Dr Chi explained. “But this activation is a double-edged sword, in that this very activation can destabilize them. They need to modulate this activation, or they will lose their stability and many of them will die. That could damage immune function.”
Dr Chi and his colleagues performed imaging studies in activated Tregs and found that autophagy was functional in the cells.
In experiments with mice, the researchers deleted Atg7 or Atg5, genes whose functions are necessary for autophagy in Tregs.
The mice showed key characteristics of Treg malfunction, including inflammatory and autoimmune disorders. The mice also more readily cleared tumors from their bodies, due to activated immune systems.
Dr Chi said that eliminating autophagy also affected the fate of Tregs.
“Once those T cells lack autophagy activity, they tend to undergo excessive cell death,” he said. “But even for the remaining surviving cells, they tend to be overly activated and lose their identity because they start to behave like non-regulatory T cells. That is why loss of autophagy in regulatory T cells produces a 2-fold effect on both survival and stability.”
Detailed analysis also revealed how the elimination of autophagy affected the basic energy-producing metabolic pathways of Tregs, compromising their function.
Dr Chi said this new understanding of autophagy’s role in Tregs could enable a 2-fold approach to immune therapy for cancers. Namely, by strengthening tumor-associated immune responses, targeting Treg autophagy could act in synergy with strategies that block autophagy in tumor cells.
In this study, the researchers used a transplanted colon cancer cell line. In further studies, they plan to explore the role of autophagy in immune reactions toward other tumor cell types to determine whether such therapies might be effective in a broad range of cancers.
The team also hopes to gain a better understanding of the detailed biochemical mechanisms regulating how autophagy connects to the cell’s metabolic pathways.