Tim-3 and PD-1 are powerful immunoinhibitory molecules involved in immune tolerance, autoimmune responses, and antitumor or antiviral immune evasion. A current model for Tim-3 regulation during immune responses suggests a divergent function, such that Tim-3 acts synergistically with TLR signaling pathways in innate immune cells to promote inflammation, yet the same molecule terminates Th1 immunity in adaptive immune cells. To better understand how Tim-3 might be functioning in innate immune responses, we examined the kinetics of Tim-3 expression in human CD14 + M/M Ф in relation to expression of IL-12, a key cytokine in the transition of innate to adaptive immunity. Here, we show that Tim-3 is constitutively expressed on unstimulated peripheral blood CD14 + monocytes but decreases rapidly upon TLR stimulation. Conversely, IL-12 expression is low in these cells but increases rapidly in CD14 + M/M Ф in correlation with the decrease in Tim-3. Blocking Tim-3 signaling or silencing Tim-3 expression led to a significant increase in TLR-mediated IL-12 production, as well as a decrease in activation-induced up-regulation of the immunoinhibitor, PD-1; TNF-α production was not altered significantly, but IL-10 production was increased. These results suggest that Tim-3 has a role as a regulator of pro- and anti-inflammatory innate immune responses. PD-1 IL-12 macrophages innate immune regulation Footnotes SEE CORRESPONDING EDITORIAL ON PAGE 183 The online version of this paper, found at www.jleukbio.org , includes supplemental information. β2M β2-microglobulin IRB Institutional Review Board LEAF low endotoxin, azide-free M/M Ф monocyte/macrophages PD-1 programmed death-1 siRNA small interfering RNA Tim-3 T cell Ig and mucin domain-3 Tregs regulatory T cells Received October 27, 2010. Revision received July 6, 2011. Accepted July 8, 2011. © 2012 Society for Leukocyte Biology Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Related articles Editorials : Ana Carrizosa Anderson Editorial: Tim-3 puts on the brakes J Leukoc Biol February 2012 91 : 183 - 185 ; doi: 10.1189/jlb.0811423 Discussion on how Tim-3 negatively regulates both innate and adaptive immune responses. Full Text Full Text (PDF) « Previous | Next Article » Table of Contents This Article Published online before print August 15, 2011 , doi: 10.1189/jlb.1010591 February 2012 Journal of Leukocyte Biology vol. 91 no. 2 189-196 » Abstract Full Text Full Text (PDF) All Versions of this Article: jlb.1010591v1 91/2/189 most recent Classifications Spotlight on Leading Edge Research Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Zhang, Y. Articles by Yao, Z. Q. PubMed PubMed citation Articles by Zhang, Y. Articles by Yao, Z. Q. Related Content Related articles in this journal Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue February 2012, 91 (2) From the Cover Editorials: Tim-3 puts on the brakes. Editorials: T cell memory, bone marrow, and aging: the good news. Spotlight on Leading Edge Research: Tim-3 regulates pro- and anti-inflammatory cytokine expression in human CD14+ monocytes. Spotlight on Leading Edge Research: The impact of aging on memory T cell phenotype and function in the human bone marrow. Reviews: Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. Reviews: Non-human primate dendritic cells. Alert me to new issues of Journal of Leukocyte Biology About JLB Submit Manuscripts Instructions for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Advertising Press Room Copyright Permissions Feedback Join SLB SLB Annual Meeting Copyright © 2012 by the Society for Leukocyte Biology Print ISSN: 0741-5400 Online ISSN: 1938-3673 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23108860-1"); pageTracker._trackPageview();

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