Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse
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-{g...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press
2010
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| Online Access: | http://hdl.handle.net/1721.1/51805 |
| _version_ | 1826206937414369280 |
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| author | Maldonado, Roberto A. Soriano, Michelle A. Perdomo, L. Carolina Sigrist, Kirsten Irvine, Darrell J. Decker, Thomas Glimcher, Laurie H. |
| author2 | Massachusetts Institute of Technology. Department of Materials Science and Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Materials Science and Engineering Maldonado, Roberto A. Soriano, Michelle A. Perdomo, L. Carolina Sigrist, Kirsten Irvine, Darrell J. Decker, Thomas Glimcher, Laurie H. |
| author_sort | Maldonado, Roberto A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:40:55Z |
| format | Article |
| id | mit-1721.1/51805 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:40:55Z |
| publishDate | 2010 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/518052022-09-28T15:29:08Z Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse Maldonado, Roberto A. Soriano, Michelle A. Perdomo, L. Carolina Sigrist, Kirsten Irvine, Darrell J. Decker, Thomas Glimcher, Laurie H. Massachusetts Institute of Technology. Department of Materials Science and Engineering Irvine, Darrell J. Irvine, Darrell J. 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. 2010-02-24T15:17:12Z 2010-02-24T15:17:12Z 2009 2008-12 Article http://purl.org/eprint/type/JournalArticle 0022-1007 http://hdl.handle.net/1721.1/51805 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. 19349465 en_US http://dx.doi.org/10.1084/jem.20082900 Journal of Experimental Medicine Attribution-Noncommercial-Share Alike 3.0 Unported http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press Publisher |
| spellingShingle | Maldonado, Roberto A. Soriano, Michelle A. Perdomo, L. Carolina Sigrist, Kirsten Irvine, Darrell J. Decker, Thomas Glimcher, Laurie H. Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse |
| title | Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse |
| title_full | Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse |
| title_fullStr | Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse |
| title_full_unstemmed | Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse |
| title_short | Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse |
| title_sort | control of t helper cell differentiation through cytokine receptor inclusion in the immunological synapse |
| url | http://hdl.handle.net/1721.1/51805 |
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