Long Non-coding RNAs in Pediatric Localized Scleroderma Profiled

Findings may offer insights into 'mechanisms' behind the disease, researchers said

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Levels of a type of immune cell called T-cells are elevated in skin biopsies from children with localized scleroderma, a new study shows.

The study showed that T-cells from pediatric localized scleroderma patients can promote scar-forming activity in skin cells when grown together in a laboratory culture. Researchers also identified nearly a dozen long RNA molecules in the skin cells affected by co-culture with T-cells.

These findings “may provide a novel insight into the mechanisms underlying pediatric localized scleroderma,” the researchers wrote.

The study, “Identification lncRNA expression profiles in pediatric localized scleroderma,” was published in the Journal of Cosmetic Dermatology.

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In localized scleroderma, abnormal inflammatory activity leads to excessive scar tissue production, ultimately causing the thickened skin patches that mark the disease. The biological mechanisms that underlie the disorder are poorly understood.

Researchers at Children’s Hospital of Fudan University, China analyzed skin biopsies taken from 21 children with localized scleroderma, as well as 21 age- and sex-matched children without skin disease.

The scientists first looked at counts of various types of immune cells in the biopsies. Levels of B-cells were similar in samples from children with or without scleroderma. However, T-cell counts were significantly increased in scleroderma patients.

More specifically, a subset of cells called CD4+ T-cells were markedly more common in scleroderma biopsies, accounting for on average more than 40% of cells in disease biopsies and less than 20% of biopsies from children without scleroderma. Another subset of T-cells called CD8+ cells also were more common in scleroderma biopsies, though the difference was somewhat less dramatic (18.3% vs. 5.3%).

CD4+ T-cells are powerful coordinators of immune activity. They can secrete a variety of different signaling molecules to help modulate the activity of other cells.

In order to better understand the role of these cells in scleroderma, the researchers co-cultured CD4+ T-cells from the biopsies with skin fibroblasts, the cells mainly responsible for producing scar tissue. Results showed fibroblasts co-cultured with CD4+ T-cells from scleroderma patients had significantly increased activity in two genes involved in fibroblast-driven scarring.

The research team then analyzed long noncoding RNAs, or lncRNAs, in these fibroblasts and biopsy samples. As the name suggests, lncRNA are long RNA molecules that don’t contain information to make protein. Instead, lncRNA play other regulatory roles in the cell, though their function is only beginning to be understood.

The analyses identified 11 lncRNAs that were abnormally expressed in the scleroderma samples: eight lncRNAs at unusually high levels and three at abnormally low levels. The researchers noted that two of the over-expressed lncRNAs, called MIR100HG and ZEB1-AS1, have previously been implicated in signaling pathways that drive scarring.

“To the best of our knowledge, this is the first report of lncRNAs profiles in pediatric localized scleroderma,” the researchers wrote, adding that further investigation into the role these molecules play in the disease “may provide a novel perspective for managing pediatric localized scleroderma.”