The human disease-associated gene ZNFX1 controls inflammation through inhibition of the NLRP3 inflammasome, 2024, Huang et al

chillier said:
Also might be worth saying the eQTL data specifically points to increased expression in brain cortex and pancreas, not really much on anywhere else. So where NLRP3 is concerned could point to microglia.
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I like the idea of microglia and or astrocytes being involved here :) They seem quite lipid sensitive like B cells too?
jnmaciuch said:
maybe! I think when the questions become “is it possible that X part of the immune system could have an impact on Y part of the immune system?” the answer will pretty much always be yes—you just need specific observations to determine whether that interaction has enough strength to really matter.
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Thanks. Understood. Fairly sure I’m on about a theory a week this last year! I’m not in a position to test anything though so will continue to hand waive and throw ideas around and hope it piques the interest of someone who is able to get evidence.
 
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hotblack said:
Fairly sure I’m on about a theory a week this last year!
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You and me both :)

I was able to find some potential connections between NLRP3 and lipid metabolism through the transcription factor SREBP (which controls lipid-related genes in a lot of cells and would be one of the more downstream switches in B cells):

It seems like SREBP is a regulator upstream of NLRP3 activation in different directions in different contexts (and these findings are in macrophages so might not translate to the B cell findings). Though both of these connections are still a bit difficult to connect potentially upregulated SREBP activity in B cells and potentially downregulated NLRP3 activation in people with the ZNFX1 variant
 
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Upon reading this paper, ZNFX1 seems to be more of a chaperone protein that suppresses NLPR3 under normal conditions until other cascades "free" NLRP3 from ZNFX1. So I'm not sure that increased expression of ZNFX1 would itself have much effect on NLRP3 activation if all other parts of the activation cascade are normal.

However, ZNFX1 might directly have a role in increasing a certain immune signal:
jnmaciuch

Thread 'Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS, 2019, Wang et al'

Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS

Wang, Yao; Yuan, Shaochun; Jia, Xin; Ge, Yong; Ling, Tao; Nie, Meng; Lan, Xihong; Chen, Shangwu; Xu, Anlong

Abstract
In the past two decades, emerging studies have suggested that DExD/H box helicases belonging to helicase superfamily 2 (SF2) play essential roles in antiviral innate immunity. However, the antiviral functions of helicase SF1, which shares a conserved helicase core with SF2, are little understood. Here we demonstrate that zinc finger NFX1-type containing 1...
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