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Review
. 2021 Nov 19;22(22):12476.
doi: 10.3390/ijms222212476.

The Role of NLRP3 Inflammasome in Lupus Nephritis

Camila Barbosa Oliveira  1   2 , Camilla Albertina Dantas Lima  2   3 , Gisele Vajgel  1 , Paula Sandrin-Garcia  2   4
Affiliations
Review

The Role of NLRP3 Inflammasome in Lupus Nephritis

Camila Barbosa Oliveira et al. Int J Mol Sci. .

Abstract

Lupus nephritis (LN) is the most frequent and severe of systemic lupus erythematosus (SLE) clinical manifestations and contributes to the increase of morbidity and mortality of patients due to chronic kidney disease. The NLRP3 (NLR pyrin domain containing 3) is a member of the NLR (NOD-like receptors), and its activation results in the production of pro-inflammatory cytokines, which can contribute to the pathogenesis of LN. In this review manuscript, we approach the relation between the NLRP3 inflammasome, SLE, and LN, highlighting the influence of genetic susceptibility of NLRP3 polymorphisms in the disease; the main functional studies using cellular and animal models of NLRP3 activation; and finally, some mechanisms of NLRP3 inhibition for the development of possible therapeutic drugs for LN.

Keywords: NLRP3; inflammasome; lupus nephritis; systemic lupus erythematosus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Possible mechanisms of NLRP3-inflammasome activation in podocytes and mononuclear phagocytes (A) and mononuclear phagocytes (B). (A): DAMPs and pro-inflammatory cytokines can activate the NLRP3 inflammasome via the NFκ-B signaling pathway. The increasing of NLRP3 transcriptions by NFκ-B induces the NLRP3-inflammasome activation. The NLRP3 inflammasome cleaves pro-IL-1β and pro-IL-18 by caspase 1. These cytokines may cause kidney damage through an induction of inflammation and polarization of Th17 cells. IL-18 can also induce the formation of NETs by neutrophils, increasing stimuli by DAMPS. (B): A second signal provided by K+ efflux and Ca2+ flux mediated by P2X7 receptor induces Ros formation, enabling NLRP3-inflammasome activation. Similarly, necrosis and fibrosis promoted by NLRP3-inflammasome activation induce Ros formation through RIP3. These mechanisms together with the formation of TGF-β appear to contribute to kidney damage in LN. NLRP3: NLR pyrin domain-containing-3; TLR: Toll-like receptor; Myd88: Myeloid differentiation factor 88; TRAF-6: TNF receptor-associated factor 6; DAMPs: Damage-associated molecular patterns; IRAK-1: Interleukin 1 receptor-associated kinase 1; IRAK-4: Interleukin 1 receptor-associated kinase 4; NFκ-B: Nuclear factor kappa B; IL: Interleukin; Th: T helper; NETs: Neutrophil extracellular traps; K+: Potassium ions; Ca2+: Calcium ions; P2X7R: P2X7.
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