Transplanted Regulatory T-cells May Reduce Inflammation in Lupus Skin Lesions

Transplanting regulatory T-cells — cells that suppress the immune system — resolved skin inflammation in a patient with systemic lupus erythematosus, Phase 1 clinical trial results show.

The study, “Adoptive Regulatory T Cell Therapy in a Patient with Systemic Lupus Erythematosus,” was published in the journal Arthritis & Rheumatism.

Regulatory T-cells (Tregs) are members of the immune system that naturally repress other immune cells and could be an effective treatment for autoimmune diseases.

An effective approach for increasing Treg numbers is transplantation, a process in which cells are collected from a patient’s blood, expanded in a lab to several million, and injected back into the patient.

But studies to date have examined the effects of Treg transplantation only in the blood, and little is known about the therapeutic effects in other tissues and organs, especially in the context of inflammation.

In an attempt to study Treg transplants in systemic lupus erythematosus patients, researchers developed a Phase 1 clinical trial (NCT02428309), meant to enroll nine patients with skin manifestations only.

“The original reason for focusing on patients with cutaneous lupus was the accessibility of skin biopsies to assess inflammation, as opposed to other tissues such as the kidney, which are considerably more difficult to obtain,” researchers wrote.

However, due to logistical reasons — mostly because patients with skin lesions often have other, more severe complications — researchers were able to recruit only one patient, a 46-year-old African American woman, into the trial.

The woman’s Tregs were effectively extracted and expanded in the lab, and were completely functional, which is evident because those cells tend to be scarce and defective in lupus patients.

The researchers did not notice significant results regarding the overall state of the skin lesions, and the transplanted cells disappeared from the blood four weeks after.

However, the researchers found interesting results when they measured the immune responses in the skin. In fact, 12 weeks after transplant, the number of skin Tregs had nearly doubled. Activated Tregs also had increased by fivefold.

This shows that the Tregs remained functional and localized to the inflamed tissues.

Additionally, the levels of interferon gamma, a molecule that acts as a trigger of the immune response, significantly decreased after the transplant. Meanwhile, interleukin-17 (IL-17) an inflammatory molecule with protective properties was highly increased.

To validate their results, researchers tested the effect of Treg transplantation in a mouse model for skin inflammation. The results were similar, with mice showing a shift from interferon-producing cells into IL-17-positive cells.

“Together, these results suggest that Treg therapy can alter the balance of [T-cell] subsets in the inflamed local site, which may have an effect on clinical manifestations of the disease,” researchers concluded.

These preliminary results need to be further validated in more patients. But they suggest that Treg transplants can help reduce inflammation in organs affected by autoimmune diseases such as lupus.