Among this group of healthy American women, we found threefold lower concentration of CCL22 in CVL samples from pregnant women than in those from non-pregnant women. This difference remained significant when corrected for multiple testing or in adjusted analysis, suggesting that pregnancy may result in reduced concentration of cervicovaginal CCL22.
The strength of this study lies in the large number of analyzed cytokines and immunomodulatory factors among healthy women. To our knowledge, this is the most comprehensive analysis of these factors in CVL of pregnant and non-pregnant women. In contrast to at least some previous studies [12–15], we did not detect differences in proinflammatory cytokines between pregnant and non-pregnant women. This could be explained by the sample size, the exclusion of women with clinical bacterial vaginosis, the relatively early collection of samples or fluctuations of these cytokines throughout pregnancy. We are however the first study that tested CCL22 concentrations in CVL.
CCL22 has previously been detected in other mucosal sites including the intestine , the lung  and the endometrium  as well as in vaginal tissue in mice , thus its presence in vaginal tissues among humans seems plausible.
Previous studies have described fluctuations of CCL22 expression in endometrium during the menstrual cycle and increases in the same tissue during early pregnancy , suggesting a control by sex hormones. While it is unclear, what caused the decreased CCL22 concentrations among pregnant women in our study, progesterone has been shown to suppress the NF-κB transcription factor , which is an activator of CCL22 expression . It is therefore possible that increased progesterone concentrations directly result in reduced CCL22 expression, which should be tested in vitro. In addition, CCL22 in our analysis was associated with a number of immunomodulatory factors, especially Ip10 and MCP-1. It was also increased shortly after coitus. Thus it is likely that there are a number of other physiological and immunological mechanisms that also influence CCL22 concentrations in CVL .
Intriguingly, CCL22 has been implied in the HIV pathogenesis in several ways. CCL22 is a T-helper cell type (TH) 2 cytokine that is highly expressed in macrophages and dendritic cells of the monocyte line  as well as in activated T-cells . It is a strong chemoattractant for leukocytes expressing the CCR4 receptor  and has been suggested to be a key regulator of innate immunity in mice . In at least some in vitro studies, CCL22 has been suggested to have HIV suppressive effects [26–29]. Such mechanisms could explain the increased risk of HIV infection with decreased CCL22 concentration. However, at least one other study suggested that CCL22 is secreted by CD16+ monocyte-derived macrophages to activate resting T-cells for HIV infection  and may therefore also increase the risk of HIV infection in certain situation. Thus further analysis of the effects of CCL22 on mucosal cytokine concentration is required.
As in all statistical analysis, we cannot exclude that differences in CVL concentrations of CCL22 are caused by chance. However, given the strong difference observed here, its possible regulation by sex hormones and its possible implication in HIV pathogens, a role of CCL22 in mediating a protection against HIV at the female genital mucosa seems plausible and should be investigated further.