CD16-positive circulating monocytes and fibrotic manifestations of systemic sclerosis

Abstract

The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p < 0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p < 0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071 Giga/L (±0.034) vs HD 0.039 Giga/L (±0.030), p < 0.01, and dSSc 0.071 Giga/L (±0.034) vs lSSc 0.048 Giga/L (±0.024), p < 0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p < 0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p < 0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p < 0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p < 0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.

Efferocytosis capacities of blood monocyte‐derived macrophages in systemic sclerosis

“…Similarly, the PI of MDM was significantly decreased in M1 HD MDM in comparison with M0 and M2a (Figure b), confirming some previous data . This downexpression of ITGβ5 both in M1 HD MDM and in SSc support the recent results from our group and others, suggesting that blood monocytes and MDM from patients with SSc not only display profibrotic properties but also share some characteristics with proinflammatory M1 MΦ …”

“…12 This downexpression of ITGb5 both in M1 HD MDM and in SSc support the recent results from our group and others, suggesting that blood monocytes and MDM from patients with SSc not only display profibrotic properties but also share some characteristics with proinflammatory M1 MΦ. 13,22,25 From a pathogenic viewpoint, the decreased efferocytosis capacities of MΦ may play a key role in the autoimmune processes associated with SSc and connective tissue diseases in general. Impaired efferocytosis is indeed a shared characteristic between SLE, Sj€ ogren syndrome 6,7 and, as suggested by our work, SSc.…”

Cytometry by time of flight identifies distinct signatures in patients with systemic sclerosis, systemic lupus erythematosus and Sjögrens syndrome

“…Additionally, the patients in this cluster had the strongest increase of circulating CXCL10 and CXCL11, chemokines previously associated with SSc disease progression and severity . These observations corroborate previous findings of increased numbers of monocytes in circulation and skin of SSc patients and an increase of CD16 + non‐classical monocytes observed in diffuse SSc patients . Further supporting the fact that monocytes might be central mediators in the pathophysiology of SSc, it was recently shown that the interferon signature is present in SSc monocytes even before the onset of overt fibrosis .…”

M-CSF and GM-CSF monocyte-derived macrophages in systemic sclerosis: the two sides of the same coin?

“…Therefore, blood MDMs’ polarisation states contrast with the macrophage signature from other tissues in SSc,3 such as lung, in which a STAT3-dependent enhanced expression of CD163 has been associated with an immune-driven pulmonary fibrosis. The results of Moreno-Moral et al on MDMs are consistent with the results of previous studies on undifferentiated peripheral blood monocytes in SSc4 in which the inflammatory component of the immune-fibrotic processes is only found in peripheral blood, illustrating this mixed (M1/M2) polarisation signature of blood monocytes and MDMs 1 3. Altogether, these results reinforce the vision of a wide and heterogeneous functional range of activated macrophages, not only depending on the disease at stake and its stage of evolution, but also on the organ of interest, highlighting the need for a more refined phenotypic characterisation of these so-called ‘M1 and M2’ macrophages in inflammatory and fibrotic disorders.…”