Immune function remodeled by mitochondrial shape: Th17 cells’ propensity for autoimmune activity is influenced by shape-shifting mitochondria

A new study focused on the immune system’s Th17 cells suggests that the shape and function of their mitochondria (the powerhouse of cells) is important in autoimmune and inflammatory disorders, such as multiple sclerosis. T helper 17 (Th17) cells are a type of CD4+ T immune cell, which collectively help make antibodies, activate enemy-eating cells and recruit more soldiers to the battlefront.

The research, led by Erika Pearce, Ph.D., at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center, suggests that learning how mitochondria impact Th17 cells is key to understanding how to control them.

The study, published Sept. 28 in the journal Nature, identifies several avenues for trying to influence the behavior of these important cells, with the goal of dampening their autoimmune activity.

When a T cell is first exposed to an enemy, it responds to signals from the enemy and the environment to become one of several types of specialized T cells, each armed with distinct functions in the immune response. While all T helper cell subtypes are crucial to the body’s fight against foreigners, their imbalance can also cause disease, including type 1 diabetes, asthma, allergies and chronic inflammation.

“If we could control T cells, we could arguably control many, if not most, infections, autoimmunities and cancers,” says Pearce, the study’s senior author and a Johns Hopkins Bloomberg Distinguished Professor in the Department of Oncology and the Department of Biochemistry and Molecular Biology.

The study began when researchers in Pearce’s laboratory, which was then at the Max Planck Institute in Freiburg, Germany, noticed a trait peculiar to Th17 cells. Among three main T effector cell types, only Th17 cells had elongated mitochondria; that is, their inner powerplants were fused together into larger structures. “That was strange because elongated mitochondria are usually seen in resting cells and not in activated cells,” says first author Francesc Baixauli, Ph.D., a former postdoctoral fellow at the Max Planck Institute.

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