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Concurrently, research has shown an impaired unfolded protein response that is mediated by cardiomyocyte-specific inositol-requiring enzyme 1 (IRE1)-X-box binding protein 1 (XBP1), which fails to suppress IFN- in TLR7/9-activated pDCs in both systemic sclerosis (SSc) and SLE, further supporting the association between dysregulated endosomal TLR responses and pathological interferon production in lupus pathogenesis [288, 289]

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Functional modifications, such as chloroquine, histidine, PEG, or PEI, have been incorporated into PLL to address these limitations