Microvesicles released by apoptotic human neutrophils suppress proliferation and IL‐2/IL‐2 receptor expression of resting T helper cells

Abstract

Membrane-coated microvesicles (MVs) have been identified as important mediators in intercellular communication. During the process of apoptosis, dying cells dynamically release MVs. Neutrophils are the most abundant type of leukocytes in the circulation. Due to their very short lifespan, it is likely that they are the source of large amounts of apoptotic cell-derived MVs. Here, we show that MVs released by apoptotic human polymorphonuclear neutrophils (apoPMN-MVs), but not the apoptotic neutrophils themselves, selectively suppress the proliferation of CD25 (IL-2Rα) CD127 (IL-7Rα) Th cells in a dose-dependent manner. In contrast, the proliferation of total T cells is not affected by MVs. Importantly, apoPMN-MVs suppress the secretion of IL-2 as well as the expression of and signaling via the IL-2 receptor (IL-2R) by CD25 CD127 Th cells. Addition of IL-7 strongly reduced the suppression of T-cell proliferation by MVs and the addition of IL-2 completely abrogated the suppressive effect. Thus, apoPMN-MVs suppressed a subset of Th cells by downregulating IL-2 and IL-2R expression and signaling. This may represent an important mechanism to prevent the activation and expansion of resting T cells in the absence of sufficient cytokine stimulation, and thereby maintaining immune tolerance.

Mesenteric lymph node stromal cell‐derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells

“…TGF-β is also associated with thymocyte-and tumor-derived EVs and involved in Treg induction [24,54,55]. Furthermore, DC-derived exosomes were shown to transfer MHCII molecules to LN-resident stromal cells, thereby inducing CD4 + T cell-mediated tolerance [44,46], and apoptotic neutrophil-derived EVs were recently reported to possess suppressive capacity on human T cells [56]. Thus, we raised the question whether FRCs can release EVs and whether mLN stromal cell-induced tolerance can be attributed to these subcellular structures.…”

Recent advances on the crosstalk between neutrophils and B or T lymphocytes

“…The latter observation suggests the existence of preferential crosstalk occurring between neutrophil and T‐cell populations depending on the disease type. Among the recently suggested mechanisms of T‐cell suppression by human neutrophils, it is worth mentioning a study in which membrane‐coated microvesicles released by apoptotic neutrophils, but not apoptotic neutrophils themselves, were shown to suppress the proliferation of a subset of CD25 − CD127 + T cells by down‐regulating IL‐2 and IL‐2 receptor expression and signalling . The existence of such a variety of immunosuppressive mechanisms might be related to the many different types of immunosuppressive neutrophil populations, conditioned by external factors.…”

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

“…For instance, neutrophil vesicles induced by N-formylmethionyl-leucyl-phenylalanine have inhibitory effects on monocyte-derived dendritic cells, which leads to an attenuated capacity to induce Tcell proliferation (20). In contrast, vesicles released by apoptotic neutrophils can selectively suppress the proliferation and IL-2 secretion of some subsets of T helper cells (21). In inflammation, neutrophil exosomes carrying leukotriene B4 upon N-formylmethionyl-leucyl-phenylalanine stimulation can elicit chemotactic activity of the resting neutrophils (22).…”