麻豆果冻传媒影音

A fuller picture of how dermal lesions develop in systemic lupus erythematosus (SLE) has been painted by researchers studying patient tissue samples, indicating that "normal-appearing" skin is actually a hotbed of proinflammatory activity.

Keratinocytes in seemingly healthy skin taken from lupus patients were found to be secreting type 1 interferons, which in turn appeared to "educate" dendritic cells that were "prominent in lesional and nonlesional skin," according to J. Michelle Kahlenberg, MD, PhD, of the University of Michigan in Ann Arbor, and colleagues.

These processes were not seen in samples from healthy controls, the group reported in .

Kahlenberg and colleagues called the interferon-driven effects on dermal immune and stromal cells "pervasive" and "pronounced in nonlesional samples" from patients, such that "normal-appearing skin of patients with [cutaneous lupus] exists in an immunologically primed, prelesional state."

Moreover, it appears possible that the "educated" dendritic cells may play a role in SLE's effects on other organ systems.

This is no small matter for lupus patients, as something like 70% develop skin manifestations. (Indeed, many cases of lupus do not appear systemic but only involve the skin.) Even when current therapies bring SLE under control, the skin lesions may remain and are hard to eradicate, the researchers noted.

Knowing that keratinocytes drive this process could eventually "provide targeted therapeutic strategies," although more research is needed to clarify what Kahlenberg's called "cell-cell communication between nonlesional and lesional" skin leading to overt inflammation and lesion development.

It was already known that lupus , but the deeper roots of what goes wrong remained to be dug out. In the new report, the researchers described a series of studies in samples taken from seven lupus patients and 14 healthy volunteers. These included RNA sequencing of patients' normal-appearing and lesional skin, histological exams to identify cell types, tests for interferons and other cytokines, ligand-receptor analyses, and studies of circulating immune cells.

One of the group's accomplishments was tracking dendritic cell transition over "pseudotime," in which different patterns of gene expression in the captured cells were presumed to . This effort produced a picture of nonclassical peripheral blood monocytes developing into CD16+ dendritic cells, during which cellular activities shifted from those related to leukocyte trafficking to autophagy and, finally, to cytokine signaling.

Limitations to the study included that of the seven lupus patients included, only one had skin manifestations without systemic illness. Such patients, the researchers acknowledged, "are as numerous as those with SLE and merit deeper investigation." Also, the study's cell-collection methods might have biased the cell types recovered, and the transcriptome analysis may have been incomplete.

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