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Hong, C.,Luckey, Megan A.,Ligons, Davinna L.,Waickman, Adam T.,Park, J.Y.,Kim, Grace Y.,Keller, Hilary R.,Etzensperger, R.,Tai, X.,Lazarevic, V.,Feigenbaum, L.,Catalfamo, M.,Walsh, Scott T.R.,Park, J. Cell Press 2014 Immunity Vol.40 No.6
The common γ-chain (γc) plays a central role in signaling by IL-2 and other γc-dependent cytokines. Here we report that activated T cells produce an alternatively spliced form of γc mRNA that results in protein expression and secretion of the γc extracellular domain. The soluble form of γc (sγc) is present in serum and directly binds to IL-2Rβ and IL-7Rα proteins on T cells to inhibit cytokine signaling and promote inflammation. sγc suppressed IL-7 signaling to impair naive T cell survival during homeostasis and exacerbated Th17-cell-mediated inflammation by inhibiting IL-2 signaling upon T cell activation. Reciprocally, the severity of Th17-cell-mediated inflammatory diseases was markedly diminished in mice lacking sγc. Thus, sγc expression is a naturally occurring immunomodulator that regulates γc cytokine signaling and controls T cell activation and differentiation.
Tinsley, Kevin W.,Hong, Changwan,Luckey, Megan A.,Park, Joo-Young,Kim, Grace Y.,Yoon, Hee-won,Keller, Hilary R.,Sacks, Andrew J.,Feigenbaum, Lionel,Park, Jung-Hyun American Society of Hematology 2013 Blood Vol.122 No.14
<P>The zinc-finger protein Ikaros is a key player in T-cell development and a potent tumor suppressor in thymocytes. To understand the molecular basis of its function, we disabled Ikaros activity in vivo using a dominant negative Ikaros transgene (DN-IkTg). In DN-IkTg mice, T-cell development was severely suppressed, and positively selected thymocytes clonally expanded, resulting in a small thymus with a heavily skewed T-cell receptor (TCR) repertoire. Notably, DN-IkTg induced vigorous proliferation concomitant to downregulation of antiapoptotic factor expression such as Bcl2. Ikaros activity was required during positive selection, and specifically at the CD4<SUP>+</SUP>CD8<SUP>lo</SUP> intermediate stage of thymocyte differentiation, where it prevented persistent TCR signals from inducing aberrant proliferation and expansion. In particular, DN-IkTg induced the accumulation of CD4 single-positive (SP) thymocytes with a developmentally transitional phenotype, and it imposed a developmental arrest accompanied by massive apoptosis. Thus, we identified an in vivo requirement for Ikaros function, which is to suppress the proliferative potential of persistent TCR signals and to promote the survival and differentiation of positively selected thymocytes.</P>
Onyedineke, Nkechi E.,Otuogbai, Timothy,Elakhame, Luckey A.,Erekaife, Joyce O. The Korean Society of Fisheries and Aquatic Scienc 2002 韓國養殖學會誌 Vol.15 No.1
We investigated the gonadosomatic index (GSI), germ cell development, reproductive cycle of the Afriean lungfish Protorierus annecteus (Owen) by histological observations and morphometric data. Samples were collected from the river Orie and its flood of Nigeria, from January to December 2000. The fish is dioecious and oviparous. Monthly changes in the gonadosomatic index (GSI) showed a similar pattern to change in the mean oocyte diameter and the reproductive cycle. The reproductive period occurred from March to July-August; the spawning period was once a year between truly and August, and the main spawning occurred in August when active and voracious feeding occurred during the rainy season. In the resting (dormant) stage after spawning, fish stopped feeding and aestivated during the dry season from December to February. The reproductive cycle of the species can be divided into five successive stages, quiescent stage (March to April), developing/maturing stage (April to lune), ripe/spawning stage (July to August), post-spawning stage (September to November), and resting (dormant) stage (December to February).