SPP1hi macrophages, NKG7 T cells, CCL5hi fibroblasts, and IgM plasma cells are dominant features of necrobiosis

Necrobiosis is a histologic term used to describe abnormal deposits of "degenerating" collagen within the skin. It can be found as an incidental finding in various granulomatous conditions, but is a hallmark of necrobiosis lipoidica (NL) and necrobiotic xanthogranuloma (NXG). There is limited prior research on necrobiosis. Here, we employed single-cell analysis of lesional and nonlesional skin to study the pathophysiology of necrobiosis. Our findings demonstrate that necrobiotic lesional skin is characterized by SPP1hi macrophages expressing MARCO; NKG7-expressing effector CD8+ T cells coexpressing CCL5, IFNG, GZMs, and PRF1; CCL5hi fibroblasts coexpressing CXCL9, diverse collagens (e.g., COL4A4, COL11A1, COL8A1), and TIMP1; and IGHM-expressing plasma cells. Integrative analysis of signaling ligands and receptor expression identified strong cell-cell communication between NKG7+ T cells, CCL5hi fibroblasts, and SPP1-expressing macrophages. In contrast, these cell populations were not dominant features of systemic sclerosis, another collagen deposition disease. Furthermore, although SPP1-expressing macrophages were detectable in sarcoidosis, IFNG-expressing T cells were a more defining feature of sarcoidosis compared with NL and NXG. From these findings, we speculate that necrobiosis results from the deposition of diverse collagens and ECM proteins through a process driven by CCL5-expressing fibroblasts and SPP1-expressing macrophages.

Authors

Institutions

Publication Details

Journal
JCI Insight
Published
2025-02-23
DOI
https://doi.org/10.1172/jci.insight.178766
Citations
2
Primary Topic
Rabies epidemiology and control
Type
article
Field-Weighted Citation Impact
2.07

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

SPP1hi macrophages, NKG7 T cells, CCL5hi fibroblasts, and IgM plasma cells are dominant features of necrobiosis

Sahiti Marella, Olga Kruglinskaya, Stephanie T. Le, Amanda Kirane et al.
2 citations
JCI Insight
Rabies epidemiology and control
2.07
article

SPP1hi macrophages, NKG7 T cells, CCL5hi fibroblasts, and IgM plasma cells are dominant features of necrobiosis

Sahiti Marella, Olga Kruglinskaya, Stephanie T. Le, Amanda Kirane, Andrea Gompers, Lauren Downing, Emanual Maverakis, Alexander A. Merleev, Iannis E. Adamopoulos, Paul W. Harms, Nikolay Yu Kuzminykh, Lam C. Tsoi, William Liakos, Johann Eli Gudjonsson, Joanne Michelle Kahlenberg, Xianying Xing, Alina I. Marusina, Allison C. Billi, S. Li, Marie‐Charlotte Brüggen, Andrey Kunitsyn
article en
2 citations

Abstract

Necrobiosis is a histologic term used to describe abnormal deposits of "degenerating" collagen within the skin. It can be found as an incidental finding in various granulomatous conditions, but is a hallmark of necrobiosis lipoidica (NL) and necrobiotic xanthogranuloma (NXG). There is limited prior research on necrobiosis. Here, we employed single-cell analysis of lesional and nonlesional skin to study the pathophysiology of necrobiosis. Our findings demonstrate that necrobiotic lesional skin is characterized by SPP1hi macrophages expressing MARCO; NKG7-expressing effector CD8+ T cells coexpressing CCL5, IFNG, GZMs, and PRF1; CCL5hi fibroblasts coexpressing CXCL9, diverse collagens (e.g., COL4A4, COL11A1, COL8A1), and TIMP1; and IGHM-expressing plasma cells. Integrative analysis of signaling ligands and receptor expression identified strong cell-cell communication between NKG7+ T cells, CCL5hi fibroblasts, and SPP1-expressing macrophages. In contrast, these cell populations were not dominant features of systemic sclerosis, another collagen deposition disease. Furthermore, although SPP1-expressing macrophages were detectable in sarcoidosis, IFNG-expressing T cells were a more defining feature of sarcoidosis compared with NL and NXG. From these findings, we speculate that necrobiosis results from the deposition of diverse collagens and ECM proteins through a process driven by CCL5-expressing fibroblasts and SPP1-expressing macrophages.

JCI InsightVol. 10(4)
Beth Israel Deaconess Medical Center (US), California Department of Food and Agriculture (US), University of Michigan (US), University Hospital of Zurich (CH), Institute of Biochemical Physics NM Emanuel (RU), Center for Rheumatology (US), University of California, Davis (US)
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Openalex Percentile: Top 16%
Rabies epidemiology and control
2.07
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.