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Proliferation of Naive CD 4 IL-27-Induced T-bet Expression but Not An Indispensable Role for STAT 1 in
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kamiya, Sadahiro Owaki, Toshiyuki Morishima, Noriko Fukai, Fumio Mizuguchi, Junichiro Yoshimoto, Takayuki |
| Copyright Year | 2004 |
| Abstract | C ytokines play pivotal roles in the regulation of various biological responses including immune responses and inflammation. Most important, cytokine signal-transduc-tion pathways are the JAKs and STATs (1–3). Immediately after receptor ligation by the cytokine, STATs are phosphorylated by JAKs, dimerized, and translocated into the nucleus, and modulate the expression of target genes. Each cytokine uses selective members of the JAK and STAT families to mediate its specific biological responses. Recently, a novel member of the IL-12 family was identified and termed IL-27 (4). IL-27 is a heterodimeric cytokine that consists of a p40-related protein, EBV-induced gene 3 (EBI3), 3 and a newly discovered IL-12 p35-related protein, p28. IL-27 is produced by activated APCs, and is able to induce proliferation of naive but not memory CD4 ϩ T cells and synergizes with IL-12 in IFN-␥ production by naive CD4 ϩ T cells (4). Previously, an orphan receptor designated type 1 cytokine receptor (TCCR; Ref. 5) or WSX-1 (6) with similarity to the IL-12R2 subunit was shown to be important for early initiation of Th1 responses. This receptor was then identified as one of the receptor subunits for IL-27, and is necessary, but not sufficient for IL-27 function (4). Notably, it is not necessary for the maintenance of Th1 responses although activation of TCCR or WSX-1 is required for the early initiation of Th1 responses (6). Therefore, IL-27 and IL-12 were considered to function sequentially in the initiation and maintenance of Th1 responses, respectively (4, 6). Consistent with this notion, it has been recently reported that IL-27 induces T-bet and subsequent IL-12R2 expression, which is a key Th1 commitment step where naive Th precursor cells commence differentiation into Th1 cells, by naive CD4 ϩ T cells through JAK1/STAT1 activation (7). However, in this report, only JAK/STAT signaling molecules that associate with one subunit of IL-27R, WSX-1/TCCR, were analyzed and identified by in vitro binding assay. The other JAK/STAT signal-ing molecules activated by IL-27 remain unexplored. In the present study, we further investigated the JAK/STAT sig-naling molecules activated by IL-27 and also the role of STAT1 in IL-27-mediated responses using STAT1-deficient mice (8, 9). In addition to JAK1 and STAT1, we have found that IL-27 activates JAK2, tyrosine kinase (TYK)2, and STAT2,-3, and-5 in naive CD4 ϩ T cells, and that STAT1 plays an indispensable role in IL-27-induced T-bet and subsequent IL-12R2 expression and MHC class I expression as well but not … |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/173/6/3871.full.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
