| First Author | Malireddi RKS | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 1068230 | PubMed ID | 36505497 |
| Mgi Jnum | J:332933 | Mgi Id | MGI:7409275 |
| Doi | 10.3389/fimmu.2022.1068230 | Citation | Malireddi RKS, et al. (2022) Determining distinct roles of IL-1alpha through generation of an IL-1alpha knockout mouse with no defect in IL-1beta expression. Front Immunol 13:1068230 |
| abstractText | Interleukin 1alpha (IL-1alpha) and IL-1beta are the founding members of the IL-1 cytokine family, and these innate immune inflammatory mediators are critically important in health and disease. Early studies on these molecules suggested that their expression was interdependent, with an initial genetic model of IL-1alpha depletion, the IL-1alpha KO mouse (Il1a-KO(line1)), showing reduced IL-1beta expression. However, studies using this line in models of infection and inflammation resulted in contrasting observations. To overcome the limitations of this genetic model, we have generated and characterized a new line of IL-1alpha KO mice (Il1a-KO(line2)) using CRISPR-Cas9 technology. In contrast to cells from Il1a-KO(line1), where IL-1beta expression was drastically reduced, bone marrow-derived macrophages (BMDMs) from Il1a-KO(line2) mice showed normal induction and activation of IL-1beta. Additionally, Il1a-KO(line2) BMDMs showed normal inflammasome activation and IL-1beta expression in response to multiple innate immune triggers, including both pathogen-associated molecular patterns and pathogens. Moreover, using Il1a-KO(line2) cells, we confirmed that IL-1alpha, independent of IL-1beta, is critical for the expression of the neutrophil chemoattractant KC/CXCL1. Overall, we report the generation of a new line of IL-1alpha KO mice and confirm functions for IL-1alpha independent of IL-1beta. Future studies on the unique functions of IL-1alpha and IL-1beta using these mice will be critical to identify new roles for these molecules in health and disease and develop therapeutic strategies. |
