# A new therapeutic approach against kidney damage in LN and COVID-19

> **NIH NIH F31** · RUSH UNIVERSITY MEDICAL CENTER · 2022 · $46,752

## Abstract

Lupus nephritis (LN) and coronavirus disease 2019 (COVID-19) both display myeloid cell dysfunction which can
lead to altered signaling resulting in tissue damage, such as kidney injury. Up to 50% of LN patients develop
chronic kidney disease (CKD) and 25% of COVID-19 patients are reported to experience acute kidney injury
(AKI) leading to long-term injury and loss of function (42,43,63). Myeloid cell dysfunction leads to secretion of
proinflammatory cytokines (IL-6, IL-1b, TNF-a) which have been shown to promote kidney damage by stimulating
immune cell infiltration and cell death (60-62). Both diseases have notable increase in circulating soluble
urokinase plasminogen activating receptor (suPAR), which have been attributed to both AKI and CKD (39,54,55).
While dysfunction has been noted in COVID-19, there is no conclusive evidence on whether this disease and
organ injury is myeloid cell-driven. Currently, there are no effective therapeutic strategies to reduce kidney
damage in these diseases despite growing concern for resulting long-term kidney dysfunction. The molecular
mechanism(s) linking TLR signaling with suPAR expression and secretion is unknown. Our group discovered
that deactivated CD11b was highly implicated in LN. CD11b is the alpha chain of the CD11b/CD18 integrin found
on myeloid cells. Further investigation displayed that CD11b activation suppressed TLR signaling and reduced
proinflammatory cytokine secretion in vivo. Furthermore, CD11b knock-in myeloid cells, from transgenic mice
that express functionally active CD11b globally, had reduced suPAR secretion in vivo after stimulation with TLR
ligands. Pharmacologic activation of CD11b by leukadherin-1 (LA1), developed in our lab, reduced suPAR
secretion. Research so far hints that suPAR expression is downstream of TLR activation, thus, suppression of
TLR signaling is a potential novel therapeutic approach against kidney injury. We hypothesize that CD11b
activation, through CD11b agonist, LA1, will suppress TLR signaling, decreasing suPAR and proinflammatory
cytokine levels, resulting in less kidney damage in patients. A multidisciplinary approach will be used to test this
hypothesis through the flowing specific aims: 1.) Assess the inflammatory response and role of CD11b in LN and
COVID-19; 2.) Define the molecular mechanism behind suPAR expression, and 3.) Determine the efficacy of
LA1 as a potential therapeutic for kidney disease in these disease contexts. To achieve the scope of this project,
extensive training in in vivo models, cell culture, molecular biology, and flow cytometry will occur. To expand my
training, several resources are available to me at Rush University Graduate College, such as the Initiative to
Maximize Student Development program and several research cores. Under the excellent mentorship of Dr.
Vineet Gupta, and with the input of distinguished collaborators, Dr. Jochen Reiser, Dr. Sanja Sever, Dr. Paul
Sanders, and Dr. Susan Quaggin, this project has the potent...

## Key facts

- **NIH application ID:** 10389224
- **Project number:** 1F31DK129006-01A1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Veronica Villanueva
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-03-04 → 2024-03-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389224

## Citation

> US National Institutes of Health, RePORTER application 10389224, A new therapeutic approach against kidney damage in LN and COVID-19 (1F31DK129006-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10389224. Licensed CC0.

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