T-cell-generated Signaling Molecule Plays Role in Development of Glomerulonephritis, Study Reports

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by Alice Melão |

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A signaling molecule produced by a type of immune T-cell plays a key role in the development of the kidney inflammation glomerulonephritis, an Australian study reports.

The molecule is interleukin-17, or IL-17. The cell that generates it is the gamma-delta (γδ) type of T-cell. And the kidney condition is myeloperoxidase (MPO) anti-neutrophil cytoplasmic autoantibody (ANCA) glomerulonephritis. The MPO part of the disease’s name refers to a protein whose loss is associated with the disease.

Researchers discovered that IL-17 promotes the development of white blood cells known as effector T-cells that attack MPO. Revving up the production of the effector T-cells contributes to an autoimmunity condition that damages the kidney’s blood vessels. An autoimmune disease is one in which the immune system attacks healthy cells instead of invaders.

Researchers published their study, “Pathogenic Role for γδ T Cells in Autoimmune Anti-Myeloperoxidase Glomerulonephritis,” in The Journal of Immunology.

Yδ T-cells are sentinels, alerting the body when they find invaders. They are also the first responders to harmful microbes.

Previous studies have demonstrated that γδ T-cells are involved in the development of autoimmune diseases such as colitis and psoriasis, and that they worsen immune injury in the kidneys.

In addition, γδ T-cells’ rapid production of IL-17 can recruit another type of white blood cell called a neutrophil. This could have implications in autoimmune diseases that target neutrophils, such as ANCA vasculitis.

“It is now recognized that innate γδ T-cells play a significant role in host defense and the generation of autoimmunity in many animal models of human autoimmune diseases,” the Monash Medical Centre researchers wrote.

They wondered if the T-cells were involved in the development of ANCA glomerulonephritis.

Using mice models lacking γδ T-cells, or the effector T-cells involved in autoimmunity, the team discovered that γδ T-cells facilitated the production of autoantibodies against MPO and the development of glomerulonephritis.

In addition, γδ T-cells played a critical role in the development of effector T-cells that target MPO. These cells are responsible for the autoimmunity mechanism in ANCA that stems from lack of MPO.

Because γδ T-cells produce IL-17, the team also wanted to know if IL-17 was involved in MPO-driven autoimmunity. They found that when IL-17 was missing, mice did not develop an MPO-related autoimmunity or glomerulonephritis.

The study demonstrated that the IL-17 produced by γδ T-cells is critical to the development of ANCA glomerulonephritis because it promotes MPO autoimmunity. The research also showed that γδ T-cells are crucial to recruiting effector T-cells to the kidneys.