IL-1R8 is an Interleukin-1R like receptor (ILR) family member that acts as a negative regulator of ILRs and TLRs signaling. Both murine and human NK cells express high levels of IL-1R8 but its functional role in this cell type has not been described so far. The results presented here show that IL-1R8 expression increases along NK cell maturation in the mouse. IL-1R8 expression and regulation in NK cells are conserved in humans, both in terms of mRNA and protein expression. Taking advantage of IL-1R8-deficient mice, we found that IL-1R8 deficiency is associated with higher frequency and absolute number of mature NK cells in blood, spleen, bone-marrow and liver. IL-1R8 deficient NK cells display increased Interferon- (IFN-) production and higher cytotoxic activity. IL-1R8 deficiency is also associated with higher expression of NK cell activating receptors (NKG2-D and DNAM-1), a more differentiated phenotype of NK cells (Ly49s and CD94) and increased activation of the mTOR pathway. Finally, to address the relevance of IL-1R8 in NK cells in vivo, we used a model of transplantable MCA-fibrosarcoma, whose metastatization in the lung is controlled by NK cells. The primary tumor similarly grew in IL-1R8-competent and deficient mice, whereas the number and dimension of lung metastasis were significantly reduced in IL-1R8-deficient mice. The depletion of NK cells in this model totally abrogated the protection from lung metastasis in IL-1R8-deficient mice. IL-1R8 plays therefore a non-redundant role in the regulation of NK cell biology and could be a crucial regulator of NK cell antitumoral activity.
Interleukin-1 receptor 8 (IL-1R8) plays a crucial role in natural killer (NK) cell differentiation and function / M. Molgora, E. Bonavita, A. Ponzetta, M. Barbagallo, G. Benigni, G. Bernardini, F. Riva, A. Santoni, A. Mantovani, C. Garlanda - In: Abstract book of the 4th European Congress of Immunology[s.l] : © ECI – European Congress of Immunology, 2015 Sep. - pp. 419 (( Intervento presentato al 4. convegno European Congress of Immunology tenutosi a Wien nel 2015.
Interleukin-1 receptor 8 (IL-1R8) plays a crucial role in natural killer (NK) cell differentiation and function
F. Riva;
2015
Abstract
IL-1R8 is an Interleukin-1R like receptor (ILR) family member that acts as a negative regulator of ILRs and TLRs signaling. Both murine and human NK cells express high levels of IL-1R8 but its functional role in this cell type has not been described so far. The results presented here show that IL-1R8 expression increases along NK cell maturation in the mouse. IL-1R8 expression and regulation in NK cells are conserved in humans, both in terms of mRNA and protein expression. Taking advantage of IL-1R8-deficient mice, we found that IL-1R8 deficiency is associated with higher frequency and absolute number of mature NK cells in blood, spleen, bone-marrow and liver. IL-1R8 deficient NK cells display increased Interferon- (IFN-) production and higher cytotoxic activity. IL-1R8 deficiency is also associated with higher expression of NK cell activating receptors (NKG2-D and DNAM-1), a more differentiated phenotype of NK cells (Ly49s and CD94) and increased activation of the mTOR pathway. Finally, to address the relevance of IL-1R8 in NK cells in vivo, we used a model of transplantable MCA-fibrosarcoma, whose metastatization in the lung is controlled by NK cells. The primary tumor similarly grew in IL-1R8-competent and deficient mice, whereas the number and dimension of lung metastasis were significantly reduced in IL-1R8-deficient mice. The depletion of NK cells in this model totally abrogated the protection from lung metastasis in IL-1R8-deficient mice. IL-1R8 plays therefore a non-redundant role in the regulation of NK cell biology and could be a crucial regulator of NK cell antitumoral activity.Pubblicazioni consigliate
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