Circulating CD14 − CD36 + peripheral blood mononuclear cells constitutively produce interleukin‐10

The impact of immune regulatory imbalance covers surprising physiological breadth. Although dominance of anti‐inflammatory cytokines such as IL‐10 is associated with reduced immune responsiveness and susceptibility to persistent infection, conditions such as cardiovascular disease and diabetes are linked to chronic inflammation and lower IL‐10 levels. An appropriate threshold for immune activation is critical for optimal protection from infection and conversely, from short‐ and long‐term side‐effects of immune effector mechanisms. To assess the possibility that IL‐10 plays a role in setting this threshold and that healthy maintenance of immune silence may involve low‐level immune suppression, we sought out and characterized human peripheral blood cells constitutively producing the immunosuppressive cytokine IL‐10. We determined the surface phenotype of circulating PBMC constitutively producing IL‐10 by surface and intracellular flow cytometry and visualized their ultrastructure by electron microscopy. The frequency of IL‐10‐producing and ‐secreting cells was estimated by ELISPOT and flow cytometry. Up to 1% of PBMC constitutively produce IL‐10. These CD14 − CD36 + CD61 + nonadherent cells expressed general markers of hematopoietic and progenitor cells (CD45 and CD7) but no stem cell, T cell, B cell, NK cell, monocytes or dendritic cell markers. Inflammation‐associated TLRs were also absent. The IL‐10‐producing cells had prominent nuclei, multiple mitochondria, and abundant rough endoplasmic reticulum. Healthy individuals have PBMC constitutively producing IL‐10. Although the lineage of these cells remains unclear, their properties and frequency suggest a potential role in homeostatic or innate immune suppression.