Immunology

A new study explains how Lymph node structural cells controls human immune responses

What’s new?

When we study the immune system it is mainly about the immune cells specifically T and B and other white blood cells. But a new study sheds light on Fibroblastic Reticular Cells (FRCs) which are the structural cells supporting immune cells and are present in lymph nodes.

A recent research from the Monash Biomedicine Discovery Institute demonstrated how Fibroblastic Reticular Cells control T cells and their response to infection.

FRC is the immunologically specialized cells found in lymphoid tissue. They have a pivotal role in T cell survival. This new work suggests that Fibroblastic Reticular Cells reduces the T cell response using 4 key mechanisms. These FRCs mechanism use pathways involving prostaglandin E2, the adenosine 2a receptor, indoleamine-2,3-dioxygenase, and transforming growth factor beta.

What did they do in their study?

In the laboratory, researchers inhibited all four FRC mechanisms using existing drugs. They found that found that once T cells are no longer suppressed by Fibroblastic Reticular Cells, they are readily able to expand and proliferate.

After that, they examined live slices of human tonsil for activation of T cell in the presence or absence of key molecules and observed that the T cells demonstrated a heightened response when Fibroblastic Reticular Cells were inhibited.

“It’s like finding out that the walls of a home control the people living in it. It is quite a surprise to most immunologists, who – understandably – have always focused on the people, or in this case, T cells,” Dr Fletcher said, who also has an honorary role at the University of Birmingham.

“This is of great significance as we are finally able to awaken the action of T cells when they are immunosuppressed in a natural setting. This is a new, clinically-relevant technique, offering a middle ground between in vitro work and human clinical trials,” Dr. Knoblich said. “It allows researchers to test the clinical relevance of their immune-targeting therapy in live human tonsil tissue, which is readily available and often discarded in surgery.”

The future perspective

These findings will help to understand the different behavior of T cell when activated in the test-tube as compared to their response in a live human tissue, which contains a complex microenvironment and Fibroblastic Reticular Cells.

“While these mechanisms of suppression are a new part of our understanding of the human biology they can also form a new platform to study metastatic cancer,” Dr. Fletcher said. “Metastasis of cancers often starts in the lymph nodes, and having a new variety of mechanisms to target can spark a number of new research platforms on the basis of these FRCs.”

 

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