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Abstract <p>Nuclear receptor subfamily 1 group H member 3 (<i>NR1H3</i>) gene of humans have important role in tuberculosis (TB). It encodes NR1H3 protein which forms part of a transcription factor regulating expression of <i>ABCA1</i> and <i>ApoE</i> genes involved in maintaining cholesterol homoeostasis in cells. TB causing bacteria <i>Mycobacterium tuberculosis</i> (MTB) depends on cholesterol for its survival in the cells. Thus, NR1H3 is regarded as crucial for early host defence against TB. The DNA binding domain of NR1H3 is encoded by exon 5 of its gene and presence of genetic variations in this region may alter its binding efficiency with target genes, subsequently resulting in altered cholesterol homeostasis and influencing host susceptibility to TB. By the modulation of NR1H3-cholesterol axis and immune system with exogenous natural NR1H3 ligands or similar compounds, they are the emerging newer drug targets within the nuclear receptor family and can be useful for host-directed therapy against TB which represents novel strategies needed for prevention and treatment of tuberculosis.</p>

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Role of Transcription Factor NR1H3 in the Pathogenesis of Tuberculosis

  • 期刊论文

  • 发表日期：

    2025年7月9日

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  • Anju Kumari,
  • Rajwinder Kaur

摘要

Abstract

Nuclear receptor subfamily 1 group H member 3 (NR1H3) gene of humans have important role in tuberculosis (TB). It encodes NR1H3 protein which forms part of a transcription factor regulating expression of ABCA1 and ApoE genes involved in maintaining cholesterol homoeostasis in cells. TB causing bacteria Mycobacterium tuberculosis (MTB) depends on cholesterol for its survival in the cells. Thus, NR1H3 is regarded as crucial for early host defence against TB. The DNA binding domain of NR1H3 is encoded by exon 5 of its gene and presence of genetic variations in this region may alter its binding efficiency with target genes, subsequently resulting in altered cholesterol homeostasis and influencing host susceptibility to TB. By the modulation of NR1H3-cholesterol axis and immune system with exogenous natural NR1H3 ligands or similar compounds, they are the emerging newer drug targets within the nuclear receptor family and can be useful for host-directed therapy against TB which represents novel strategies needed for prevention and treatment of tuberculosis.