chronic inflammation

Researchers Explore How Activation of Integrin Segment Suppresses Inflammation in Lupus Nephritis

The signaling molecule CD11b may protect against lupus nephritis (LN) and may suppress inflammation, according to new data presented at the American Society of Nephrology 2021 Kidney Week.

LN and reduced integrin function may result from mutations in the gene that encodes CD11b, the α chain of integrin CD11b/CD18. CD11b has an important role in cell signaling. 

Researchers at Rush University previously determined that CD11b suppresses proinflammatory signaling that depends on toll-like receptor. The inflammatory mediator interleukin-1β (IL-1β), which is produced by myeloid cells, is downstream of toll-like receptor. According to the researchers, a better understanding of how CD11b affects IL-1β could lead to the development of new therapies for inflammatory diseases such as LN.

To determine whether CD11b activation suppresses toll-like receptor-dependent proinflammatory signaling by controlling IL-1β, or influences IL-1β through another mechanism, or does both, the researchers performed in-vitro assays by using primary macrophages. They treated cells with toll-like receptor agonists, IL-1β protein, or IL-1β antibody and assessed changes in protein expression by using Western blot and changes in proinflammatory cytokine levels by using ELISA.

They also conducted complementary in-vivo studies by using a genetically modified knock‑in mouse model of CD11b activation. They determined the effect of CD11b activation on circulating IL-1β by comparing this effect in wild-type mice with that in CD11b knock-out and CD11b knock-in mice. 

As a result, they found that stimulation of toll-like receptor increased levels of IL-1β and that CD11b activation significantly reduced levels of IL-1β both in-vitro and in-vivo. “Using these models, we have identified a possible link between CD11b activation and IL-1β secretion in myeloid cells,” the researchers concluded. They added that these findings suggest “a novel mechanism for controlling inflammation in glomerular diseases” such as LN. 

The researchers added that, in murine models of systemic lupus erythematosus and LN, a significant decrease in IL-1β results when CD11b is activated by either genetic modification or medication. According to the researchers, these findings also indicate that CD11b activation may protect against LN.

Additional studies are being conducted to define the exact molecular mechanism of action of CD11b and to clarify its effect on signaling pathways and inflammation associated with LN.

—Ellen Kurek


Villanueva V, Li X, Jimenez V, Gupta V. CD11b activation suppresses pro‑inflammatory IL-1β in myeloid cells and protects against lupus nephritis. Paper presented at: ASN 2021 Kidney Week; November 4-7, 2021; Virtual.