Disease relevance of Il15ra

• Using a model of 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity (CHS) we found that, as compared with wild-type mice, IL-15 receptor alpha chain (IL-15Ralpha)-deficient mice showed significantly less ear swelling [1].
• More importantly, both anti-IL-15 antibody- and recombinant IL-15 receptor alpha-treated Borrelia-vaccinated and -infected mice were free of major histopathologic indications of arthritis, including hyperplasia, hypertrophy, and vilus formation of the synovium [2].

High impact information on Il15ra

• The IL-15 receptor alpha subunit (IL-15Ralpha) mediates high-affinity binding of IL-15, a pleiotropic cytokine implicated in the development of innate immune cells [3].
• Thus, IL-15Ralpha has pleiotropic roles in immune development and function, including the positive maintenance of lymphocyte homeostasis [3].
• IL-15Ralpha-/- mice are markedly lymphopenic despite grossly normal T and B lymphocyte development [3].
• We also found that hypernociception induced by ovalbumin (OVA) in OVA-immunized mice was significantly diminished by treatment with sIL-15Ralpha (soluble IL-15 receptor alpha-chain), bosentan, BQ123, or indomethacin [4].
• Naive CD8 T cell development required IL-15R alpha expression by both bone marrow-derived and parenchymal cells, whereas memory-phenotype CD8 T cells required IL-15R alpha expression only by hematopoietic cells [5].

Biological context of Il15ra

• Further analyses demonstrated that IL-15Ralpha(+) BM-derived cells were crucial in driving memory CD8 T-cell division in the spleen while both parenchymal and BM-derived cells promoted memory cell division in the lung [6].
• Moreover, Ab-mediated neutralization studies revealed that endogenous IL-15 activity regulated Mphi activation with kinetics similar to that seen in response to exogenously added IL-15: suppressor activity increased over time in correlation with IL-15R alpha gene expression [7].
• These findings suggest that YopM interferes with innate immunity by causing depletion of NK cells, possibly by affecting the expression of IL-15 receptor alpha and IL-15 [8].

Anatomical context of Il15ra

• Transregulation of memory CD8 T-cell proliferation by IL-15Ralpha+ bone marrow-derived cells [6].
• Differential roles for IL-15R alpha-chain in NK cell development and Ly-49 induction [9].
• Endothelial cells were found to express the IL-15R alpha chain and the IL-2/15R beta and common gamma chains [10].

Regulatory relationships of Il15ra

• We show here the effects of IL-15 on the proliferation and maintenance of murine gamma delta i-IEL in vitro. gamma delta i-IEL constitutively expressed a high level of IL-15 receptor alpha mRNA and proliferated in response to IL-15 more vigorously than alpha beta i-IEL [11].
• We determined that both the number of CD8(+) T cells infiltrating the affected skin and the production of CCL5/RANTES by antigen-stimulated CD8(+) T cells were decreased in IL-15Ralpha(-/-) mice [1].

Other interactions of Il15ra

• These results indicate that transpresentation of IL-15 by IL-15Ralpha on BM-derived cells mediates the basal proliferation of memory CD8 T cells [6].
• Large intestine intraepithelial lymphocytes from Apc+/+ and Apc+/Min mice and their modulation by indigestible carbohydrates: the IL-15/IL-15R alpha complex and CD4+ CD25+ T cells are the main targets [12].

Analytical, diagnostic and therapeutic context of Il15ra

• Selective blockade of IL-15 by soluble IL-15 receptor alpha-chain enhances cardiac allograft survival [13].
• Soluble IL-15 receptor alpha-chain administration prevents murine collagen-induced arthritis: a role for IL-15 in development of antigen-induced immunopathology [14].

References