OBJECTIVE: Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines, with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. METHODS: Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and body mass index. Samples were stained for the macrophage marker CD68, and the average proportions of ATMs, crown-like structures (periadipocyte aggregates of 3 or more ATMs), and fibrosis were compared between groups. RESULTS: The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA than in non-RA samples (37.7 versus 21.3%, respectively; P < 0.001), and the adjusted average number of crown-like structures was more than 1.5-fold higher in the RA group than in controls (0.58 versus 0.23 crown-like structure/high-power field, respectively; P = 0.001). ATMs were significantly more abundant in early RA and in those with anti-cyclic citrullinated peptide seropositivity. Users of methotrexate, leflunomide, and tumor necrosis factor inhibitors had a significantly lower proportion of ATMs compared with nonusers. Crown-like structures were significantly higher in patients with rheumatoid factor seropositivity and in those with C-reactive protein levels ≥10 mg/liter, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole-body insulin resistance, but not with serum lipids. CONCLUSIONS: ATMs and crown-like structures were more abundant in RA patients and were associated with systemic inflammation, autoimmunity, and whole-body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and crown-like structures associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation.
OBJECTIVE: Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines, with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. METHODS: Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and body mass index. Samples were stained for the macrophage marker CD68, and the average proportions of ATMs, crown-like structures (periadipocyte aggregates of 3 or more ATMs), and fibrosis were compared between groups. RESULTS: The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA than in non-RA samples (37.7 versus 21.3%, respectively; P < 0.001), and the adjusted average number of crown-like structures was more than 1.5-fold higher in the RA group than in controls (0.58 versus 0.23 crown-like structure/high-power field, respectively; P = 0.001). ATMs were significantly more abundant in early RA and in those with anti-cyclic citrullinated peptide seropositivity. Users of methotrexate, leflunomide, and tumor necrosis factor inhibitors had a significantly lower proportion of ATMs compared with nonusers. Crown-like structures were significantly higher in patients with rheumatoid factor seropositivity and in those with C-reactive protein levels ≥10 mg/liter, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole-body insulin resistance, but not with serum lipids. CONCLUSIONS: ATMs and crown-like structures were more abundant in RA patients and were associated with systemic inflammation, autoimmunity, and whole-body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and crown-like structures associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation.
Authors: Beatriz Y Hanaoka; Matthew P Ithurburn; Cody A Rigsbee; S Louis Bridges; Douglas R Moellering; Barbara Gower; Marcas Bamman Journal: Arthritis Care Res (Hoboken) Date: 2019-01-04 Impact factor: 4.794
Authors: Emma K Haley; Mederbek Matmusaev; Imtiyaz N Hossain; Sean Davin; Tammy M Martin; Joerg Ermann Journal: PLoS One Date: 2021-05-13 Impact factor: 3.240
Authors: Iván Arias-de la Rosa; Alejandro Escudero-Contreras; Miriam Ruiz-Ponce; Laura Cuesta-López; Cristóbal Román-Rodríguez; Carlos Pérez-Sánchez; Patricia Ruiz-Limón; Rocío Guzman- Ruiz; Fernando Leiva-Cepas; Juan Alcaide; Pedro Segui; Chamaida Plasencia; Ana Martinez-Feito; Pilar Font; María C Ábalos; Rafaela Ortega; María M Malagón; Francisco J Tinahones; Eduardo Collantes-Estévez; Chary López-Pedrera; Nuria Barbarroja Journal: iScience Date: 2022-08-06
Authors: Iván Arias de la Rosa; Alejandro Escudero-Contreras; Miriam Ruiz-Ponce; Cristóbal Román-Rodríguez; Carlos Pérez-Sánchez; María Del Carmen Ábalos-Aguilera; Rafaela Ortega-Castro; Juan Alcaide; Mora Murri; Pilar Font; Jerusalem Calvo-Gutiérrez; Maria Luque-Tevar; Alejandra Maria Patiño-Trives; Rocío Guzmán-Ruiz; Maria Del Mar Malagón; Francisco José Tinahones; Eduardo Collantes-Estévez; Chary López-Pedrera; Nuria Barbarroja Journal: Front Immunol Date: 2021-10-13 Impact factor: 7.561