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CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis.

Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C - Arthritis Res. Ther. (2016)

Bottom Line: In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role.Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054, Erlangen, Germany.

ABSTRACT

Background: The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters.

Method: Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test.

Results: The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.

Conclusion: M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

No MeSH data available.


Related in: MedlinePlus

Distribution of T regulatory cells and their correlation with macrophage subtypes. The number of forkhead box protein P3 (FoxP3) + regulatory T cells was analyzed in International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus classes and correlation tested with numbers of total CD68+, M1-like, M2a-like and M2c-like macrophages in the tubulointerstitium. a Glomerular FoxP3+ cells in ISN/RPS class II–V. b Tubulointerstitial FoxP3+ cells in ISN/RPS classs II–V. c Correlation between FoxP3+ cells and tubulointerstitial total CD68+ macrophages. d Correlation between FoxP3+ cells and tubulointerstitial M1-like macrophages. e Correlation between FoxP3+ cells and tubulointerstitial M2a-like macrophages. f Correlation between FoxP3+ cells and tubulointerstitial M2c-like macrophages. Significant differences and correlation are marked by asterisks (*p < 0.05; **p < 0.01)
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Fig7: Distribution of T regulatory cells and their correlation with macrophage subtypes. The number of forkhead box protein P3 (FoxP3) + regulatory T cells was analyzed in International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus classes and correlation tested with numbers of total CD68+, M1-like, M2a-like and M2c-like macrophages in the tubulointerstitium. a Glomerular FoxP3+ cells in ISN/RPS class II–V. b Tubulointerstitial FoxP3+ cells in ISN/RPS classs II–V. c Correlation between FoxP3+ cells and tubulointerstitial total CD68+ macrophages. d Correlation between FoxP3+ cells and tubulointerstitial M1-like macrophages. e Correlation between FoxP3+ cells and tubulointerstitial M2a-like macrophages. f Correlation between FoxP3+ cells and tubulointerstitial M2c-like macrophages. Significant differences and correlation are marked by asterisks (*p < 0.05; **p < 0.01)

Mentions: FoxP3+ regulatory T cells were detected in low numbers in glomeruli (Fig. 7a). More FoxP3+ cells were found in the tubulointerstitium (Fig. 7b). In both compartments the greatest number of FoxP3+ cells was found in SLE ISN/RPS class IV biopsies (Fig. 7a, b). FoxP3+ cells always co-located with macrophages, e.g., CD163+ M2c-like macrophages (Fig. 2d). However, the number of FoxP3+ T regulatory cells was positively correlated with all investigated macrophage subpopulations, M1-like (Fig. 7d), M2a-like (Fig. 7e), M2c-like (Fig. 7f) and consequently the number of total CD68+ macrophages in the tubulointerstitial compartment (Fig. 7c).Fig. 7


CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis.

Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C - Arthritis Res. Ther. (2016)

Distribution of T regulatory cells and their correlation with macrophage subtypes. The number of forkhead box protein P3 (FoxP3) + regulatory T cells was analyzed in International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus classes and correlation tested with numbers of total CD68+, M1-like, M2a-like and M2c-like macrophages in the tubulointerstitium. a Glomerular FoxP3+ cells in ISN/RPS class II–V. b Tubulointerstitial FoxP3+ cells in ISN/RPS classs II–V. c Correlation between FoxP3+ cells and tubulointerstitial total CD68+ macrophages. d Correlation between FoxP3+ cells and tubulointerstitial M1-like macrophages. e Correlation between FoxP3+ cells and tubulointerstitial M2a-like macrophages. f Correlation between FoxP3+ cells and tubulointerstitial M2c-like macrophages. Significant differences and correlation are marked by asterisks (*p < 0.05; **p < 0.01)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835936&req=5

Fig7: Distribution of T regulatory cells and their correlation with macrophage subtypes. The number of forkhead box protein P3 (FoxP3) + regulatory T cells was analyzed in International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus classes and correlation tested with numbers of total CD68+, M1-like, M2a-like and M2c-like macrophages in the tubulointerstitium. a Glomerular FoxP3+ cells in ISN/RPS class II–V. b Tubulointerstitial FoxP3+ cells in ISN/RPS classs II–V. c Correlation between FoxP3+ cells and tubulointerstitial total CD68+ macrophages. d Correlation between FoxP3+ cells and tubulointerstitial M1-like macrophages. e Correlation between FoxP3+ cells and tubulointerstitial M2a-like macrophages. f Correlation between FoxP3+ cells and tubulointerstitial M2c-like macrophages. Significant differences and correlation are marked by asterisks (*p < 0.05; **p < 0.01)
Mentions: FoxP3+ regulatory T cells were detected in low numbers in glomeruli (Fig. 7a). More FoxP3+ cells were found in the tubulointerstitium (Fig. 7b). In both compartments the greatest number of FoxP3+ cells was found in SLE ISN/RPS class IV biopsies (Fig. 7a, b). FoxP3+ cells always co-located with macrophages, e.g., CD163+ M2c-like macrophages (Fig. 2d). However, the number of FoxP3+ T regulatory cells was positively correlated with all investigated macrophage subpopulations, M1-like (Fig. 7d), M2a-like (Fig. 7e), M2c-like (Fig. 7f) and consequently the number of total CD68+ macrophages in the tubulointerstitial compartment (Fig. 7c).Fig. 7

Bottom Line: In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role.Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054, Erlangen, Germany.

ABSTRACT

Background: The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters.

Method: Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test.

Results: The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.

Conclusion: M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

No MeSH data available.


Related in: MedlinePlus