Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse
Name
Maldonado-2009-Control of T helper.pdf
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3.04 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Maldonado, Roberto A.
Soriano, Michelle A.
Perdomo, L. Carolina
Sigrist, Kirsten
Irvine, Darrell J.
Decker, Thomas
Glimcher, Laurie H.
Date Issued
2009
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
Maldonado, Roberto A. et al. “Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse.” The Journal of Experimental Medicine 206.4 (2009): 877-892.
Version
Final published version
Abstract
The antigen recognition interface formed by T helper precursors (Thps) and antigen-presenting cells (APCs), called the immunological synapse (IS), includes receptors and signaling molecules necessary for Thp activation and differentiation. We have recently shown that recruitment of the interferon-{gamma} receptor (IFNGR) into the IS correlates with the capacity of Thps to differentiate into Th1 effector cells, an event regulated by signaling through the functionally opposing receptor to interleukin-4 (IL4R). Here, we show that, similar to IFN-{gamma} ligation, TCR stimuli induce the translocation of signal transducer and activator of transcription 1 (STAT1) to IFNGR1-rich regions of the membrane. Unexpectedly, STAT1 is preferentially expressed, is constitutively serine (727) phosphorylated in Thp, and is recruited to the IS and the nucleus upon TCR signaling. IL4R engagement controls this process by interfering with both STAT1 recruitment and nuclear translocation. We also show that in cells with deficient Th1 or constitutive Th2 differentiation, the IL4R is recruited to the IS. This observation suggest that the IL4R is retained outside the IS, similar to the exclusion of IFNGR from the IS during IL4R signaling. This study provides new mechanistic cues for the regulation of lineage commitment by mutual immobilization of functionally antagonistic membrane receptors.
MIT Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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Attribution-Noncommercial-Share Alike 3.0 Unported
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DOI of Published Version
http://dx.doi.org/10.1084/jem.20082900
