Abstract
Natural killer (NK) cells and dendritic cells (DCs) are two innate immune cells that are critical in regulating innate and adaptive immunity. Cellular functions and migratory responses of NK or DC can be further regulated in NK-DC crosstalk that involves multiple cytokine signals and/or direct cell-cell contacts. Semaphorin-3E (Sema-3E) is a member of a large family of Semaphorin proteins that play diverse regulatory functions in different biological systems upon its binding to the cognate receptors. However, possible role(s) of Sema-3E on the regulation of NK-cell functions has not been elucidated. Here, we first demonstrated that DC and NK cells expressed Sema-3E and its receptors, respectively. To formally address the importance of DC-derived Sema-3E in regulating NK-cell migration, we compared in vitro migratory responses of activated NK cells (aNKs) toward different conditioned media of DCs (immature, lipopolysaccharide- or Poly I:C-stimulated) derived from Sema-3E+/+ or Sema-3E−/− mice. We observed that aNKs exhibited enhanced migrations toward the conditioned medium of the immature Sema-3E−/− DC, when compared with that of the immature Sema-3E+/+ DC. Addition of exogenous recombinant Sema-3E to the conditioned medium of the Sema-3E−/− immature DC (iDC) abrogated such enhanced NK-cell migration. Our current work revealed a novel role of Sema-3E in limiting NK-cell migrations toward iDC in NK-DC crosstalk.
Highlights
Natural killer (NK) cells are members of the emerging family of innate lymphoid cells that play important roles in innate immunity and tissue remodeling [1, 2]
In the examination of the putative role of Sema-3E in NK-dendritic cells (DCs) crosstalk, we first established the expression of Sema-3E mRNA in DC and NK cells (“resting” ex vivo, IL-2 activated) by PCR
We demonstrated that the Sema-3E primers and the PCR conditions were Sema-3E-specific, as we detected no Sema-3E mRNA expression in the Sema-3E−/− immature DC (iDC) cells (KO), whereas high level of Sema-3E mRNA expression was detected in the 4T1 cells (Figure 1A)
Summary
Natural killer (NK) cells are members of the emerging family of innate lymphoid cells that play important roles in innate immunity and tissue remodeling [1, 2] They migrate to peripheral or inflamed tissues to exert their immune-surveillance functions [3]. DCs are professional antigen-presenting cells that engage T cell receptor with the cognate MHC/Peptide complex (Signal 1) and co-stimulatory molecules (Signal 2) to regulate optimal T cell activation. Depending on their maturation and activation states, DC acquires specific ability to induce either immunological tolerance or differentiation of distinct T cell subsets [14, 16]. Regulation of DC maturation/functions by NK cells presents another indirect mechanism for NK cells to coordinate innate and adaptive immune responses in vivo [18,19,20]
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