Newly Discovered Pathway Suggests How T-Cells Can Help Drive MS, IBD and Type 1 Diabetes

Research By Aakanksha Jain, PhD, Chandrashekhar Pasare, DVM, PhD

Post Date: December 17, 2019 | Publish Date: Dec. 17, 2019

Autoimmunity Acceleration

Autoimmunity Acceleration

These cell flow cytometry graphs were used by immuno-biologists to illustrate the physical and chemical characteristics of T cells that help drive autoimmunity in mice. Part of a study published by Nature Immunity, the left graph shows resting effector T cell (featured in black) before autoimmune processes are triggered. The right graph shows changes (in red) once the T cells start to produce a pro-inflammatory protein called TNF (tumor necrosis factor). This begins downstream autoimmune processes linked to several diseases in people.

In a study published online Dec. 17, 2019, in Nature Immunology, scientists at Cincinnati Children’s report finding a key molecular pathway that may open doors to better treatments for autoimmune diseases.

The study, in mice, shows how auto-reactive T cells, macrophage and dendritic cells in the immune system work through two other molecules—TNF (tumor necrosis factor) and FasL (fas ligand)—to produce overabundant amounts of IL-1b (cytokine interleukin-1 beta).

This excess amount of IL-1b protein appears to feed a T-cell-driven inflammation process found in diseases including multiple sclerosis (MS), type 1 diabetes and inflammatory bowel disease (IBD).

“This means our findings have two previously unknown implications,” Pasare explained. “We show for the first time that IL-1b can be made in the absence of infection and that T cells are major drivers of IL-1b in an autoimmune setting.”

The findings suggest that targeting the TNF and FasL pathway of IL-1b production is more likely to be an effective way of treating auto-immune diseases in humans. However, it remains too early to determine whether these mouse-based findings will translate safely and effectively to humans.

Read more about the research

Publication Information

Original Title:T cells instruct myeloid cells to produce inflammasome-independent IL-1β and cause autoimmunity
Published in:Nature Immunology
Publish date:Dec. 17, 2019

Read the study

Research By

  • Aakanksha Jain, PhD

    Aakanksha Jain, PhD

    former member of the Pasare laboratory

  • Chandrashekhar Pasare, DVM, PhD

    Chandrashekhar Pasare, DVM, PhD

    co-director of the Center for Inflammation and Tolerance

    Dr. Pasare's laboratory is involved in studying the Toll-like receptor signaling pathway in cells of the innate immune system and also investigating the mechanisms by which these receptors regulate adaptive immune responses.