CD16+ Monocyte Subset Was Enriched and Functionally Exacerbated in Driving T-Cell Activation and B-Cell Response in Systemic Lupus Erythematosus

Zhu, Huaqun; Hu, Fanlei; Sun, Xiaolin; Zhang, Xiaoying; Zhu, Lei; Liu, Xu; Li, Xue; Xu, Liling; Shi, Lianjie; Gan, Yuzhou; Su, Yin

doi:10.3389/fimmu.2016.00512

Cited by 57 publications

(41 citation statements)

References 51 publications

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“…Notably, different from well‐accepted concepts that immature monocytes enhance the inflammation whereas mature monocytes down‐regulate inflammation , mature monocytes in SLE patients have been suggested to possess a pathogenic role to promote lupus disease by enhancing pathogenic T cell responses . The results of the present study support this notion, as our cell population of interest, which is derived from mature monocytes, appears to be proinflammatory and contributes to disease pathogenesis in LN.…”

Section: Discussionsupporting

confidence: 71%

Renal-infiltrating CD11c+ cells are pathogenic in murine lupus nephritis through promoting CD4+ T cell responses

Liao

Ren

Reihl

et al. 2017

Clinical and Experimental Immunology

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Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE), causing morbidity and mortality in 40-60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone mice. These cells may play important pathogenic or regulatory roles in situ to promote or sustain LN. Here, using lupus-prone mouse models, we showed the pathogenic role of a kidney-infiltrating CD11c myeloid cell population in LN. These CD11c cells accumulated in the kidneys of lupus-prone mice as LN progressed. Surface markers of this population suggest their dendritic cell identity and differentiation from lymphocyte antigen 6 complex (Ly6C) mature monocytes. The cytokine/chemokine profile of these renal-infiltrating CD11c cells suggests their roles in promoting LN, which was confirmed further in a loss-of-function in-vivo study by using an antibody-drug conjugate (ADC) strategy targeting CX CR1, a chemokine receptor expressed highly on these CD11c cells. However, CX CR1 was dispensable for the homing of CD11c cells into lupus nephritic kidneys. Finally, we found that these CD11c cells co-localized with infiltrating T cells in the kidney. Using an ex- vivo co-culture system, we showed that renal-infiltrating CD11c cells promoted the survival, proliferation and interferon-γ production of renal-infiltrating CD4 T cells, suggesting a T cell-dependent mechanism by which these CD11c cells promote LN. Together, our results identify a pathogenic kidney-infiltrating CD11c cell population promoting LN progression, which could be a new therapeutic target for the treatment of LN.

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Section: Discussionsupporting

confidence: 71%

Renal-infiltrating CD11c+ cells are pathogenic in murine lupus nephritis through promoting CD4+ T cell responses

Liao

Ren

Reihl

et al. 2017

Clinical and Experimental Immunology

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“…In the Ad26 prime, the accumulation of CD16 + monocyte-derived de novo-differentiated CD163 + CX3CR1 + macrophages 20 in the lymph nodes and the high counts of T H 17 cells in the mucosa may have created an inflammatory innate response that negated the protective effect of the mucosal antibodies to V2. The association of CD16 + monocytes and increased T H 17 cell differentiation has also been observed in other inflammatory conditions 36,37,53 . Ad26 uses CD46 as a receptor whose engagement induces autophagy 54 , a strategy used by adenoviruses to increase their replication 55,56 .…”

Section: Discussionmentioning

confidence: 52%

“…Collectively, these data support that the DNA and ALVAC prime regimens elicited CD4 + T H 2 cell responses that correlated with mucosal antibodies to V2 and the recruitment and ability of mucosal NKp44 + cells to produce IL-17. By contrast, the Ad26 prime was associated with the skewing of the CD4 + T cell response at mucosal sites towards a more inflammatory T H 17 cell response, an event that was probably related to the increased frequency of CX3CR1 + CD163 + macrophages and IL-23 in tissue, as observed in other inflammatory conditions 36,37 .…”

Section: Resultsmentioning

confidence: 84%

HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition

Vaccari

Fourati

Gordon

et al. 2018

Nat Med

104

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Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)–SIV, DNA–SIV and Ad26–SIV vaccine prime modalities together with two ALVAC–SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14+CD16− monocytes, gut-homing CCR5-negative CD4+ T helper 2 (TH2) cells and antibodies to variable region 2 correlated with a decreased risk of SIVmac251 acquisition. By contrast, signal transducer and activator of transcription 3 activation in CD16+ monocytes was associated with an increased risk of virus acquisition. The Ad26 prime regimen induced the accumulation of CX3CR1+CD163+ macrophages in lymph nodes and of long-lasting CD4+ TH17 cells in the gut and lungs. Our data indicate that the selective engagement of monocyte subsets following a vaccine prime influences long-term immunity, uncovering an unexpected association of CD14+ innate monocytes with a reduced risk of SIVmac251 acquisition.

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“…CD14 + CD16 + and CD14 + CD16 − monocyte subsets might possess different functions in RA. Our previous study showed that CD14 + CD16 + monocytes in patients with systemic lupus erythematosus showed inflammatory phenotype, with increased CD80, CD86, HLA-DR, and CX3CR1, which could promote Th17 response [ 30 ]. IL-17 is a pro-inflammatory cytokine mainly produced by CD4 + T cells and plays a critical role in RA synovitis [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

CD14+CD16− monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK

Xue

Zhu

et al. 2020

Arthritis Res Ther

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Background Monocytes as precursors of osteoclasts in rheumatoid arthritis (RA) are well demonstrated, while monocyte subsets in osteoclast formation are still controversial. Tyro3 tyrosine kinase (Tyro3TK) is a member of the receptor tyrosine kinase family involved in immune homeostasis, the role of which in osteoclast differentiation was reported recently. This study aimed to compare the osteoclastic capacity of CD14+CD16+ and CD14+CD16− monocytes in RA and determine the potential involvement of Tyro3TK in their osteoclastogenesis. Methods Osteoclasts were induced from CD14+CD16+ and CD14+CD16− monocyte subsets isolated from healthy control (HC) and RA patients in vitro and evaluated by tartrate-resistant acid phosphatase (TRAP) staining. Then, the expression of Tyro3TK on CD14+CD16+ and CD14+CD16− monocyte subsets in the peripheral blood of RA, osteoarthritis (OA) patients, and HC were evaluated by flow cytometry and qPCR, and their correlation with RA patient clinical and immunological features was analyzed. The role of Tyro3TK in CD14+CD16− monocyte-mediated osteoclastogenesis was further investigated by osteoclast differentiation assay with Tyro3TK blockade. Results The results revealed that CD14+CD16− monocytes were the primary source of osteoclasts. Compared with HC and OA patients, the expression of Tyro3TK on CD14+CD16− monocytes in RA patients was significantly upregulated and positively correlated with the disease manifestations, such as IgM level, tender joint count, and the disease activity score. Moreover, anti-Tyro3TK antibody could inhibit Gas6-mediated osteoclast differentiation from CD14+CD16− monocytes in a dose-dependent manner. Conclusions These findings indicate that elevated Tyro3TK on CD14+CD16− monocytes serves as a critical signal for osteoclast differentiation in RA.

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CD16+ Monocyte Subset Was Enriched and Functionally Exacerbated in Driving T-Cell Activation and B-Cell Response in Systemic Lupus Erythematosus

Cited by 57 publications

References 51 publications

Renal-infiltrating CD11c+ cells are pathogenic in murine lupus nephritis through promoting CD4+ T cell responses

Renal-infiltrating CD11c+ cells are pathogenic in murine lupus nephritis through promoting CD4+ T cell responses

HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition

CD14+CD16− monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK

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