Soluble γc cytokine receptor suppresses IL-15 signaling and impairs iNKT cell development in the thymus.
The soluble γc protein (sγc) is a naturally occurring splice isoform of the γc cytokine receptor that is produced by activated T cells and inhibits γc cytokine signaling. Here we show that sγc expression is also highly upregulated in immature CD4+CD8+thymocytes but then downregulated in mature thymocytes. These results indicate a developmentally controlled mechanism for sγc expression and suggest a potential role for sγc in regulating T cell development in the thymus. Indeed, sγc overexpression resulted in significantly reduced thymocyte numbers and diminished expansion of immature thymocytes, concordant to its role in suppressing signaling by IL-7, a critical γc cytokine in early thymopoiesis. Notably, sγc overexpression also impaired generation of iNKT cells, resulting in reduced iNKT cell percentages and numbers in the thymus. iNKT cell development requires IL-15, and we found that sγc interfered with IL-15 signaling to suppress iNKT cell generation in the thymus. Thus, sγc represents a new mechanism to control cytokine availability during T cell development that constrains mature T cell production and specifically iNKT cell generation in the thymus.
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Joo-Young
JY
Park
Department of Anatomy, Pusan National University School of Medicine, Yangsan 626-870, South-Korea.
Yuna
Y
Jo
Department of Anatomy, Pusan National University School of Medicine, Yangsan 626-870, South-Korea.
Eunhee
E
Ko
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Megan A
MA
Luckey
Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, South-Korea.
Yoo Kyoung
YK
Park
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South-Korea.
Se-Ho
SH
Park
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Jung-Hyun
JH
Park
Department of Anatomy, Pusan National University School of Medicine, Yangsan 626-870, South-Korea.
Changwan
C
Hong
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D057809:HEK293 Cells; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
C569274:IL15 protein, human; D019409:Interleukin-15; D018121:Receptors, Cytokine