Abstract
An association between inducible costimulator ligand (ICOS-L) expression and interleukin (IL)-10 production by dendritic cells (DCs) has been commonly found in infectious disease. DCs with higher ICOS-L expression and IL-10 production are reportedly more efficient in inducing regulatory T cells (Tregs). Here we use the Chlamydia muridarum (Cm) lung infection model in IL-10 knockout (KO) mice to test the relationship between IL-10 production and ICOS-L expression by DCs. We examined ICOS-L expression, the development of T-cell subsets, including Treg, Th17 and Th1 cell, in the background of IL-10 deficiency and its relationship with ICOS-L/ICOS signaling after infection. Surprisingly, we found that the IL-10 KO mice exhibited significantly higher ICOS-L expression by DCs. Moreover, IL-10 KO mice showed lower Tregs but higher Th17 and Th1 responses, but only the Th17 response depended on ICOS signaling. Consistently, most of the Th17 cells were ICOS⁺, whereas most of the Th1 cells were ICOS⁻ in the infected mice. Furthermore, neutralization of IL-17 in IL-10 KO mice significantly exacerbated lung infection. The data suggest that ICOS-L expression on DC may be negatively regulated by IL-10 and that ICOS-L expression on DC in the presence or absence of IL-10 costimulation may promote Treg or Th17 response, without significant impact on Th1.
Highlights
In addition to T-cell receptor (TCR) engagement, the initiation of optimal T-cell response requires costimulatory signals
We first compared inducible costimulator ligand (ICOS-L) expression on the dendritic cells (DCs) of IL-10 KO and WT mice before and after Chlamydia muridarum (Cm) infection
DCs enriched by magnetic cell sorting buffer (MACS) columns were double stained with anti-CD11c and anti-Inducible costimulator (ICOS)-L monoclonal antibodies (mAbs) and analyzed by flow cytometry
Summary
In addition to T-cell receptor (TCR) engagement, the initiation of optimal T-cell response requires costimulatory signals. ICOS can be expressed by different T-cell subsets, but appears more on Th2 and regulatory T cells [5,6,7,8,9,10,11]. Expression of surface costimulatory molecules and production of cytokines by DCs are critically important for the modulating effect of DCs on T-cell function and development of T-cell subsets. Akbari et al [13] reported the importance of ICOS–ICOS-L interaction in the development of regulatory T cells (Tregs). We reported that chlamydial lung infection and systemic mycobacterial infection can generate DCs that exhibit increased surface expression of ICOS-L and increased IL-10 production [14,15]. We found that the DCs, which coexpressed higher ICOS-L and IL-10 after infection, were more efficient in inducing Tregs to allergen exposure [14,15]
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