Biomedicine Xagena

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Immunoregulation without immunossupression: the promise of low-dose Interleukin-2

The immune system is composed of numerous interacting cell populations with distinct functions. As for any system, it is ( it has to be ) tightly regulated. Failure of regulation leads notably to inflammatory and autoimmune diseases.

A simplistic paradigm is that the balance between effector and regulatory T cells ( Teff and Treg ) plays a major role in dosing/regulating the immune response.
Likewise, autoimmune diseases are caused by an imbalance that favors the effector arm of the immune response, whether caused by an increase in Teff or a defect in Tregs numbers/functions.

While blocking Teff with immunosuppressant has long been the only therapeutic option to correct this imbalance, it now appears that activating/expanding Tregs may achieve the same purpose without the toxicity and side effects of immunosuppression.

Researchers at Pitié-Salpêtrière Hospital ( paris, France ) have recently reported that Interleukin-2 ( IL-2 ), which has so far been used at high-dose and with high toxicity to stimulate Teffs in cancer, could be used at well tolerated low-doses to stimulate Tregs in vivo in humans,
They report that IL-2 can be given chronically without immunosuppression in mice. This opens broad applications for treatment of a wide range of chronic diseases, from inflammatory to autoimmune diseases, and more broadly for tolerance induction.

The concepts and tools of cell and gene therapy will be useful for these developments, and conversely IL-2 induced immunoregulation may help control adverse immune reactions in cell and gene therapy. ( Xagena )

Klatzmann D, Human Gene Therapy, 2013