The function of Tim-3 as an inhibitory receptor in T cell immune regulation has been well documented to date (1, 2). However, the positive immunoregulatory function of Tim-3 has also been implicated by studies (3). Recently, we constructed a CHO cell line expressing full-length Tim-3, designated as Tim-3-CHO, which highly expressed Tim-3. We cultured bone marrow-derived immature DCs in the presence of prefixed Tim-3-CHO, and found that DCs were induced and became mature by upregulating CD80, CD86, and MHC class II. This process could be prevented by the addition of Tim-3 Ab. Moreover, we found that Tim-3 stimulation enhanced the presentation of tumor antigen by DCs. Thus, Tim-3 seems to have a positive role in immunoregulation.

Systemic lupus erythematosus (SLE), one of the most common autoimmune disorders, affects numerous organ systems. Although most patients with SLE lead full, active, and healthy lives, the induction of disease activity (flares) might be catastrophic. It is well known that pregnancy may increase the frequency of SLE flares (4). However, the underlying mechanism still remains elusive. In our recent work (5) we showed that Tim-3 is upregulated in innate immune cells during pregnancy, and the increased Tim-3 is involved in the maintenance of systemic immunity. This study not only further reinforces the concept of Tim-3 as a positive immune regulator but also implies that the upregulation of Tim-3 expression could facilitate SLE flares during the pregnancy of SLE patients. We agreed with the comment “TIM-3 may be implicated in the pathogenesis of SLE and TIM-3 could be a potential therapeutic target for systemic lupus erythematosus” by Dr. Pan et al. Actually, our unpublished data showed that Tim-3 is more highly expressed in SLE pregnant women, compared with normal counterparts. Therefore, Tim-3 in pregnancy may protect the body from infection, and has a potential to trigger autoimmune response.

We also tested other clinical settings besides pregnancy. Interestingly, we found that Tim-3 is quickly upregulated in innate immune cells during infection. This may be explained by the observation that Tim-3 stimulation promotes the phagocytosis of pathogens. On the basis of these findings and previous studies, we propose that Tim-3 crucially regulates immune responses at different phases: Tim-3 acts as a positive regulator by enhancing DC maturation, antigen presentation, and pathogen clearance at the innate stage; but as a negative regulator by limiting excessive T cell responses and avoiding autoimmunity at the adaptive stage.

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