Disease relevance of Il2rg

• Lymphohaematopoietic abnormalities and systemic lymphoproliferative disorder in interleukin-2 receptor gamma chain-deficient mice [1].
• Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor gamma chain (gamma(c)), which is mutated in humans with X-linked severe combined immunodeficiency [2].
• BACKGROUND & AIMS: Mice that have a truncated mutation of the common cytokine receptor gamma chain (CR gamma -/Y) are known to spontaneously develop colitis [3].
• We have begun to dissect the cellular requirements for generation of immunity against enteric infection by Listeria monocytogenes using a novel T(-) B(-) NK(-) mouse strain (mice double deficient for the common cytokine receptor gamma-chain (gamma(c)) and the recombinase-activating gene-2 (RAG2/gamma(c) mice) [4].
• Expression of the mouse interleukin-2 receptor gamma chain in insect cells using a baculovirus expression vector--comparison with the human common gamma chain [5].

High impact information on Il2rg

• Studies with monoclonal antibodies specific for the IL-2 receptor gamma chain showed that the gamma chain participates in the functional high-affinity receptor complexes for IL-7 that are involved in the differentiation of T and B cells [6].
• Pro-thymocyte expansion by c-kit and the common cytokine receptor gamma chain is essential for repertoire formation [7].
• The common cytokine receptor gamma chain (gamma(c)) is an indispensable subunit for the formation of lymphoid-related cytokine receptors, including IL-7 and IL-15 receptors, that mediate nonredundant or critical signals for the differentiation of T and B cells and natural killer (NK) cells, respectively [8].
• Mutations in the receptor tyrosine kinase c-kit and the common cytokine receptor gamma chain (gamma c) reduce cellularity, but are permissive for thymocyte development [7].
• In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg(-/-) mice [9].

Biological context of Il2rg

• The gene (Il2rg) is well conserved between mouse and man with respect to overall structure and size, and contains regions of high conservation in the promoter region as well [10].
• Il2rg maps to mouse X chromosome region 40, in a region of synteny with human Xq12-13 [10].
• We have also characterized the genomic structure of the murine Tslpr gene which shows that in addition to primary sequence homology, it shares a common genomic organization of coding exons with the murine IL-2 receptor common gamma chain (Il2rg) [11].
• Interleukin 2 receptor gamma chain (gamma(c)) knockout mice show less regularity in estrous cycle but achieve normal pregnancy without fetal compromise [12].
• The common cytokine receptor gamma chain plays an essential role in regulating lymphoid homeostasis [13].

Anatomical context of Il2rg

• Role of common cytokine receptor gamma chain (gamma(c))- and Jak3-dependent signaling in the proliferation and survival of murine mast cells [14].
• Cytokines, including those that signal via receptors using the common cytokine receptor gamma-chain (gamma(c)), have been implicated at various stages of NK cell development [15].
• Bone marrow from LTalpha-deficient mice was unable to initiate development of CP or isolated lymphoid follicles (ILF) after transfer to CD132-null mice lacking CP and ILF [16].
• Expression of the common cytokine receptor gamma chain by murine dendritic cells including epidermal Langerhans cells [17].
• The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor gamma chain (gamma(c)) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development [18].

Associations of Il2rg with chemical compounds

• Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes [6].
• The small subunit of calpain, a calcium-dependent cysteine protease, was found to interact with the cytoplasmic domain of the common cytokine receptor gamma chain (gammac) in a yeast two-hybrid interaction trap assay [19].
• These results, together with its relative abundance and apparent molecular weight, suggest that p64 probably corresponds to the soluble form of a variable surface glycoprotein from T. evansi [20].
• Mild acid treatment only slightly decreased the immunorecognition of p64, demonstrating that another relevant cross-reacting epitope, different than the inositol-1,2-cyclic phosphate of the cross-reacting determinant, must exist in p64 [20].

Physical interactions of Il2rg

• Interleukin (IL)-7 interactions with its cognate receptor complex (IL-7Ralpha coupled to the common cytokine receptor gamma chain, gammac) play a dominant role in early thymopoiesis [21].

Regulatory relationships of Il2rg

• The role of the common cytokine receptor gamma-chain in regulating IL-2-dependent, activation-induced CD8+ T cell death [22].
• DESIGN: Using plasmid vectors containing the IL-2R alpha chain gene under the control of a cytomegalovirus promoter or the IL-2R gamma chain gene under the control of a Rous sarcoma virus promoter, the IL-2R genes were transferred by lipofection into SCCHN cell lines [23].

Other interactions of Il2rg

• In contrast, blocking the common cytokine receptor gamma-chain (gamma c) prevented Bcl-2 induction and augmented AICD [22].
• Distinct roles for signals relayed through the common cytokine receptor gamma chain and interleukin 7 receptor alpha chain in natural T cell development [24].
• IL-15Ralpha, CD122 (IL-2/15Rbeta), and common gamma-chains (CD132) were expressed in both populations, whereas IL-21Ralpha was expressed only in CD11b(-) BM cells [25].
• Impaired peripheral deletion of activated T cells in mice lacking the common cytokine receptor gamma-chain: defective Fas ligand expression in gamma-chain-deficient mice [26].
• Colitis in mice lacking the common cytokine receptor gamma chain is mediated by IL-6-producing CD4+ T cells [3].

Analytical, diagnostic and therapeutic context of Il2rg

• Common cytokine receptor gamma chain (gamma c)-dependent cytokines: understanding in vivo functions by gene targeting [27].
• Bone marrow transplantation of NK cell-negative mice due to null mutations in the recombination-activating gene (Rag) 2/common cytokine receptor gamma-chain (Rag2(-/-)gamma(c)(-/-)) genes indicated that uNK cells originate from the bone marrow and require IL-15 to develop [28].
• The IL2R gamma chain was also affected by THC treatment in that Northern blotting studies showed a drug-induced decrease in the cellular level of gamma chain mRNA [29].
• PBL from healthy human volunteers were administered i.p. into IL-2 receptor gamma-chain-disrupted NOD-SCID mice [IL-2R(-/-) NOD-SCID] [30].

References