The CD14^brightCD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population

Abstract

Objective. Circulating monocytes contain a subpopulation of CD14؉CD16؉ cells; this subpopulation of cells has been described to be proinflammatory and to have an increased frequency in rheumatoid arthritis (RA). New evidence suggests that this subpopulation can be further subdivided into CD14 dim CD16؉ and CD14 bright CD16؉ cells. The aim of this study was to determine which of the two CD16؉ monocyte subpopulations is expanded in patients with RA and to investigate their possible role in disease pathogenesis.Methods. The frequencies of monocyte subpopulations in the peripheral blood of healthy donors and patients with RA were determined by flow cytometry. Monocyte subpopulations were sorted and cocultured with CD4؉ T cells. Cytokines were determined in the supernatant, and Th17 cell frequencies were measured by flow cytometry.Results. In comparison with the other monocyte subpopulations, CD14 bright CD16؉ cells showed higher HLA-DR and CCR5 expression and responded with higher tumor necrosis factor production to direct cell contact with preactivated T cells. They were observed at increased frequencies in the peripheral blood of patients with RA, while CD14 dim CD16؉ monocyte frequencies were not increased. CD14 bright CD16؉ cells were extremely potent inducers of Th17 cell expansion in vitro. Their frequency in the peripheral blood of patients with RA correlated closely with Th17 cell frequencies determined ex vivo.Conclusion. This study is the first to provide a link between the increased frequency of the CD14 bright CD16؉ monocyte subpopulation in RA and the expansion of Th17 cells, which are likely to have a role in the pathogenesis of autoimmunity.

Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response

“…Therefore, their role in malignant disease seems ambiguous, as this subset is capable of stimulating tumor angiogenesis on the one hand, but may also exert antitumor effects on the other hand by the production of pro-inflammatory cytokines such as TNF-a, IL-1b and IL-6 and by antigen presentation. 11,24 In the present study with mCRC patients, intermediate monocytes in blood seem to reflect a systemic immunological response to chemotherapy. Thus, their increase in circulation may be induced by a systemic spillover of mediators released by the therapeutically damaged tumor tissue.…”

“…Previous studies have shown an increase of intermediate monocytes in other inflammatory conditions including rheumatoid arthritis and sepsis. 24,25 Thus, evaluation of monocyte subsets in tumor patients certainly has to take into consideration potential coexisting morbidities. However, the therapy-triggered rise in intermediate monocytes as compared to pretreatment values may identify a tumor-related effect and hence serve as a novel marker for the prediction of treatment response.…”

Pivotal Role for CD16+ Monocytes in Immune Surveillance of the Central Nervous System

“…In summary, alterations in the composition of the mobile CSF monocyte pool may reflect a shift of CD16 + monocytes from the periphery to sites of inflammation. Such a compartmentalization, which is typical for MS, may account for the difference in monocyte subgroup distributions in other autoimmune diseases (7)(8)(9)(10)(11)(12)(13)(14)(15). CD16 + non-classical so-called patrolling monocytes exert important functions in the peripheral immune compartment.…”

“…In these studies, it was demonstrated that the expansion of CD16 + monocytes is driven by the intermediate monocyte subset (9)(10)(11) and that these CD16 + monocytes actively shape T cell responses by favoring Th17 differentiation (9). Accordingly, it has been suggested that CD16 + monocytes play a pivotal role in the pathophysiology of autoimmune diseases.…”

Infliximab therapy increases the frequency of circulating CD16+ monocytes and modifies macrophage cytokine response to bacterial infection

“…Peripheral blood monocytes have been divided into three distinct subsets according to CD14 and CD16 marker expression [18,20,21] + monocyte subsets, particularly the intermediate subset, have been associated with inflammatory functions [20] and are known to be the major producers of inflammatory cytokines such as TNF and interleukin (IL)-1β [22,23]. It was reported that, in CD patients with active disease, CD16…”