Skip to main content
Erschienen in: Rheumatology International 4/2012

01.04.2012 | Original Article

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

Erschienen in: Rheumatology International | Ausgabe 4/2012

Einloggen, um Zugang zu erhalten

Abstract

With the purpose of contributing to a better knowledge of the APCs functional activity in SLE, we evaluated the distribution and functional ability to produce pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12) of peripheral blood (PB) monocytes and DC (tDC), particularly myeloid (mDC) and CD14−/lowCD16+ DC subpopulations comparing them with those obtained from healthy individuals. The study was performed in 34 SLE patients with diverse disease activity scores (SLEDAI) and 13 healthy age- and sex-matched controls (NC). Our results show an overall decrease in absolute number and relative frequency of tDC in SLE patients with active disease when compared to those with inactive disease and NC, although this decrease did not seem to have an effect on the distribution of PB DC subsets. The monocytes number in SLE patients was similar to those found in NC, whereas a higher frequency of monocytes producing cytokines as well as the amount of each cytokine per cell found without stimulation was particularly observed in those patients with active disease. After stimulation, we observed a higher frequency of IL-12-producing monocytes in active SLE patients. On the other hand, we found among DCs higher frequencies of cytokine-producing CD14−/lowCD16+ DCs and a higher amount of cytokines produced per cell, particularly in active disease. These findings support an increased production of inflammatory cytokines by APCs in active SLE, mostly associated with alterations in CD14−/lowCD16+ DC subset homeostasis that might contribute to explain the dynamic role of these cells in disease pathogenesis.
Literatur
4.
Zurück zum Zitat Mozaffarian N, Wiedeman AE, Stevens AM (2008) Active systemic lupus erythematosus is associated with failure of antigen-presenting cells to express programmed death ligand-1. Rheumatology (Oxford) 47:1335–1341. doi:10.1093/rheumatology/ken256 CrossRef Mozaffarian N, Wiedeman AE, Stevens AM (2008) Active systemic lupus erythematosus is associated with failure of antigen-presenting cells to express programmed death ligand-1. Rheumatology (Oxford) 47:1335–1341. doi:10.​1093/​rheumatology/​ken256 CrossRef
6.
Zurück zum Zitat Pertovaara M, Hasan T, Raitala A, Oja SS, Yli-Kerttula U, Korpela M et al (2007) Indoleamine 2, 3-dioxygenase activity is increased in patients with systemic lupus erythematosus and predicts disease activation in the sunny season. Clin Exp Immunol 150:274–278. doi:10.1111/j.1365-2249.2007.03480.x PubMedCrossRef Pertovaara M, Hasan T, Raitala A, Oja SS, Yli-Kerttula U, Korpela M et al (2007) Indoleamine 2, 3-dioxygenase activity is increased in patients with systemic lupus erythematosus and predicts disease activation in the sunny season. Clin Exp Immunol 150:274–278. doi:10.​1111/​j.​1365-2249.​2007.​03480.​x PubMedCrossRef
7.
Zurück zum Zitat Grage-Griebenow E, Flad HD, Ernst M (2001) Heterogeneity of human peripheral blood monocyte subsets. J Leukoc Biol 69:11–20PubMed Grage-Griebenow E, Flad HD, Ernst M (2001) Heterogeneity of human peripheral blood monocyte subsets. J Leukoc Biol 69:11–20PubMed
10.
Zurück zum Zitat Leon B, Lopez-Bravo M, Ardavin C (2005) Monocyte-derived dendritic cells. Semin Immunol 17:313–318PubMedCrossRef Leon B, Lopez-Bravo M, Ardavin C (2005) Monocyte-derived dendritic cells. Semin Immunol 17:313–318PubMedCrossRef
11.
Zurück zum Zitat Almeida J, Bueno C, Alguero MC, Sanchez ML, de Santiago M, Escribano L et al (2001) Comparative analysis of the morphological, cytochemical, immunophenotypical, and functional characteristics of normal human peripheral blood lineage(−)/CD16(+)/HLA-DR(+)/CD14(-/lo) cells, CD14(+) monocytes, and CD16(−) dendritic cells. Clin Immunol 100:325–338. doi:10.1006/clim.2001.5072 PubMedCrossRef Almeida J, Bueno C, Alguero MC, Sanchez ML, de Santiago M, Escribano L et al (2001) Comparative analysis of the morphological, cytochemical, immunophenotypical, and functional characteristics of normal human peripheral blood lineage(−)/CD16(+)/HLA-DR(+)/CD14(-/lo) cells, CD14(+) monocytes, and CD16(−) dendritic cells. Clin Immunol 100:325–338. doi:10.​1006/​clim.​2001.​5072 PubMedCrossRef
13.
Zurück zum Zitat Ziegler-Heitbrock HW, Fingerle G, Strobel M, Schraut W, Stelter F, Schutt C et al (1993) The novel subset of CD14+/CD16+ blood monocytes exhibits features of tissue macrophages. Eur J Immunol 23:2053–2058. doi:10.1002/eji.1830230902 PubMedCrossRef Ziegler-Heitbrock HW, Fingerle G, Strobel M, Schraut W, Stelter F, Schutt C et al (1993) The novel subset of CD14+/CD16+ blood monocytes exhibits features of tissue macrophages. Eur J Immunol 23:2053–2058. doi:10.​1002/​eji.​1830230902 PubMedCrossRef
14.
Zurück zum Zitat Thomas R, Lipsky PE (1994) Human peripheral blood dendritic cell subsets. Isolation and characterization of precursor and mature antigen-presenting cells. J Immunol 153:4016–4028PubMed Thomas R, Lipsky PE (1994) Human peripheral blood dendritic cell subsets. Isolation and characterization of precursor and mature antigen-presenting cells. J Immunol 153:4016–4028PubMed
18.
20.
Zurück zum Zitat Theofilopoulos AN, Koundouris S, Kono DH, Lawson BR (2001) The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1/Th2 paradigm in autoimmunity. Arthritis Res 3:136–141. doi:10.1186/ar290 PubMedCrossRef Theofilopoulos AN, Koundouris S, Kono DH, Lawson BR (2001) The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1/Th2 paradigm in autoimmunity. Arthritis Res 3:136–141. doi:10.​1186/​ar290 PubMedCrossRef
21.
Zurück zum Zitat Ding D, Mehta H, McCune WJ, Kaplan MJ (2006) Aberrant phenotype and function of myeloid dendritic cells in systemic lupus erythematosus. J Immunol 177:5878–5889PubMed Ding D, Mehta H, McCune WJ, Kaplan MJ (2006) Aberrant phenotype and function of myeloid dendritic cells in systemic lupus erythematosus. J Immunol 177:5878–5889PubMed
23.
Zurück zum Zitat Robak E, Smolewski P, Wozniacka A, Sysa-Jedrzejowska A, Stepien H, Robak T (2004) Relationship between peripheral blood dendritic cells and cytokines involved in the pathogenesis of systemic lupus erythematosus. Eur Cytokine Netw 15:222–230PubMed Robak E, Smolewski P, Wozniacka A, Sysa-Jedrzejowska A, Stepien H, Robak T (2004) Relationship between peripheral blood dendritic cells and cytokines involved in the pathogenesis of systemic lupus erythematosus. Eur Cytokine Netw 15:222–230PubMed
24.
Zurück zum Zitat Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725PubMedCrossRef Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725PubMedCrossRef
25.
Zurück zum Zitat Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRef Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRef
26.
Zurück zum Zitat Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640. doi:10.1002/art.1780350606 PubMedCrossRef Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640. doi:10.​1002/​art.​1780350606 PubMedCrossRef
27.
Zurück zum Zitat Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed
30.
Zurück zum Zitat Gigante A, Amoroso D, Ferri F, Gianni C, Coppolino G, Papa A et al (2006) Systemic lupus erythematosus and renal involvement: which role of citokines expression? Eur Rev Med Pharmacol Sci 10:223–228PubMed Gigante A, Amoroso D, Ferri F, Gianni C, Coppolino G, Papa A et al (2006) Systemic lupus erythematosus and renal involvement: which role of citokines expression? Eur Rev Med Pharmacol Sci 10:223–228PubMed
31.
32.
Zurück zum Zitat Cederblad B, Blomberg S, Vallin H, Perers A, Alm GV, Ronnblom L (1998) Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha—producing cells. J Autoimmun 11:465–470. doi:10.1006/jaut.1998.0215 PubMedCrossRef Cederblad B, Blomberg S, Vallin H, Perers A, Alm GV, Ronnblom L (1998) Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha—producing cells. J Autoimmun 11:465–470. doi:10.​1006/​jaut.​1998.​0215 PubMedCrossRef
33.
Zurück zum Zitat Vallin H, Blomberg S, Alm GV, Cederblad B, Ronnblom L (1999) Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells. Clin Exp Immunol 115:196–202. doi:10.1046/j.1365-2249.1999.00772.x PubMedCrossRef Vallin H, Blomberg S, Alm GV, Cederblad B, Ronnblom L (1999) Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells. Clin Exp Immunol 115:196–202. doi:10.​1046/​j.​1365-2249.​1999.​00772.​x PubMedCrossRef
35.
Zurück zum Zitat Jin O, Kavikondala S, Sun L, Fu R, Mok MY, Chan A et al (2008) Systemic lupus erythematosus patients have increased number of circulating plasmacytoid dendritic cells, but decreased myeloid dendritic cells with deficient CD83 expression. Lupus 17:654–662. doi:10.1177/0961203308089410 PubMedCrossRef Jin O, Kavikondala S, Sun L, Fu R, Mok MY, Chan A et al (2008) Systemic lupus erythematosus patients have increased number of circulating plasmacytoid dendritic cells, but decreased myeloid dendritic cells with deficient CD83 expression. Lupus 17:654–662. doi:10.​1177/​0961203308089410​ PubMedCrossRef
36.
Zurück zum Zitat Li Y, Lee PY, Sobel ES, Narain S, Satoh M, Segal MS et al (2009) Increased expression of FcgammaRI/CD64 on circulating monocytes parallels ongoing inflammation and nephritis in lupus. Arthritis Res 11:R6. doi:10.1186/ar2590 Li Y, Lee PY, Sobel ES, Narain S, Satoh M, Segal MS et al (2009) Increased expression of FcgammaRI/CD64 on circulating monocytes parallels ongoing inflammation and nephritis in lupus. Arthritis Res 11:R6. doi:10.​1186/​ar2590
37.
Zurück zum Zitat Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115:407–417. doi:10.1172/JCI200523025 PubMed Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115:407–417. doi:10.​1172/​JCI200523025 PubMed
Metadaten
Titel
Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus
Publikationsdatum
01.04.2012
Erschienen in
Rheumatology International / Ausgabe 4/2012
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-010-1709-6

Weitere Artikel der Ausgabe 4/2012

Rheumatology International 4/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.