| First Author | Bednarczyk M | Year | 2022 |
| Journal | Cells | Volume | 11 |
| Issue | 14 | PubMed ID | 35883631 |
| Mgi Jnum | J:342303 | Mgi Id | MGI:7325745 |
| Doi | 10.3390/cells11142188 | Citation | Bednarczyk M, et al. (2022) beta2 Integrins on Dendritic Cells Modulate Cytokine Signaling and Inflammation-Associated Gene Expression, and Are Required for Induction of Autoimmune Encephalomyelitis. Cells 11(14) |
| abstractText | Heterodimeric beta2 integrin surface receptors (CD11a-d/CD18) are specifically expressed by leukocytes that contribute to pathogen uptake, cell migration, immunological synapse formation and cell signaling. In humans, the loss of CD18 expression results in leukocyte adhesion deficiency syndrome (LAD-)1, largely characterized by recurrent severe infections. All available mouse models display the constitutive and ubiquitous knockout of either alpha or the common beta2 (CD18) subunit, which hampers the analysis of the cell type-specific role of beta2 integrins in vivo. To overcome this limitation, we generated a CD18 gene floxed mouse strain. Offspring generated from crossing with CD11c-Cre mice displayed the efficient knockdown of beta2 integrins, specifically in dendritic cells (DCs). Stimulated beta2-integrin-deficient splenic DCs showed enhanced cytokine production and the concomitantly elevated activity of signal transducers and activators of transcription (STAT) 1, 3 and 5, as well as the impaired expression of suppressor of cytokine signaling (SOCS) 2-6 as assessed in bone marrow-derived (BM) DCs. Paradoxically, these BMDCs also showed the attenuated expression of genes involved in inflammatory signaling. In line, in experimental autoimmune encephalomyelitis mice with a conditional DC-specific beta2 integrin knockdown presented with a delayed onset and milder course of disease, associated with lower frequencies of T helper cell populations (Th)1/Th17 in the inflamed spinal cord. Altogether, our mouse model may prove to be a valuable tool to study the leukocyte-specific functions of beta2 integrins in vivo. |
