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This article is part of the Research Topic

Molecular Mechanisms of Proteinuria

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Front. Med. | doi: 10.3389/fmed.2018.00052

CD11b Activity Modulates Pathogenesis of Lupus Nephritis

  • 1Department of Internal Medicine, Rush University Medical Center, United States
  • 2Independent Researcher, United States

Lupus Nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) with unclear etiology and limited treatment options. Immune cell infiltration into the kidneys, a hallmark of LN, triggers tissue damage and proteinuria. CD11b, the α-chain of integrin receptor CD11b/CD18 (also known as αMβ2, Mac-1 and CR3), is highly expressed on the surface of innate immune cells, including macrophages and neutrophils. Genetic variants in the human ITGAM gene, which encodes for CD11b, are strongly associated with susceptibility to SLE, LN and other complications of SLE. CD11b modulates several key biological functions in innate immune cells, including cell adhesion, migration and phagocytosis. CD11b also modulates other signaling pathways in these cells, such as the Toll-like receptor (TLR) signaling pathways, that mediate generation of type I interferons (IFN I), a key pro-inflammatory cytokine and circulating biomarker in SLE and LN patients. However, how variants in ITGAM gene contribute to disease pathogenesis has not been completely established. Here, we provide an overview of CD11b modulated mechanisms and the functional consequences of the genetic variants that can drive disease pathogenesis. We also present recent insights from studies after pharmacological activation of CD11b. These studies offer novel mechanisms for development of therapeutics for LN, SLE and other autoimmune diseases.

Keywords: Lupus Nephritis, CD11b, ITGAM, type I interferon, Leukadherin-1

Received: 16 Dec 2017; Accepted: 13 Feb 2018.

Edited by:

Sandra Merscher, University of Miami, United States

Reviewed by:

Ana C. Zenclussen, Medizinische Fakultät, Universitätsklinikum Magdeburg, Germany
David A. Fulcher, Australian National University, Australia  

Copyright: © 2018 Khan, Khan and Gupta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. Samia Q. Khan, Rush University Medical Center, Department of Internal Medicine, 1735 W. Harrison St., Cohn 714, Chicago, 60612, IL, United States, samia_khan@rush.edu
PhD. Vineet Gupta, Rush University Medical Center, Department of Internal Medicine, 1735 W. Harrison St., Cohn 714, Chicago, 60612, IL, United States, vineet_gupta@rush.edu