Skip to main content
. Author manuscript; available in PMC: 2023 Aug 1.
Published in final edited form as: Trends Immunol. 2022 Jul 13;43(8):640–656. doi: 10.1016/j.it.2022.06.004

Table 2.

X-linked genes or miRNAs with a potential role in anti-TB immunity

Gene Product Location Function Human polymorphism phenotype Mutant mouse TB phenotype Ref.
TLR7 $ Xp22

  • Recognition of ssRNA

 ↑ HCV and HIV-1 - [97–99]
TLR8 $ Xp22

  • Recognition of ssRNA

 ↑ TB susceptibility - [90,91]
CYBB $ Xp21

  • NADPH oxidase

 MSMD with CGD Susceptible [100,101]
CD40L $ Xq26

  • Expressed mainly on activated T cells

  • CD40-CD40L binding triggers cytokine and chemokine production

 Together with TLR8 & IRAKI polymorphic variants, ↑ male-susceptibility to pulmonary TB Similar to wild type but impaired granuloma formation [102,103]
IRAK1 $ Xq28

  • IL-1 receptor-associated kinase 1

  • Regulates TLR and IL-1R mediated signaling

 Autoimmune diseases such as SLE, systemic sclerosis, rheumatoid arthritis, etc. - [104]
CXorf21 $ Xp21

  • TLR adaptor interacting with SLC15A4 on lysosomes

 Sexual dimorphism in SLE - [105]
NEMO Xq28

  • NF-κB essential modulator

 MSMD - [106]
FOXP3 Xp11

  • Transcriptional regulator for Treg cells

  • inhibits IFN-γ production and T-cell effector function

 ↑ female susceptibility to TB, ↑ viral susceptibility - [107,108]
IL13RA1$ & RA2 Xq24

  • IL-13 receptor a1 and a2

 Atopic disease Unknown* [109–112]
CXCR3 $ Xq13

  • C-X-C motif chemokine receptor 3

 Male-bias and pleuritis in SLE Resistant to TB [113,114]
KDM6a $ Xp11

  • Lysine-specific demethylase 6A

 Bladder cancer, B cell lymphoma - [115]
miR-223 Xq13

  • PMN recruitment

 Rheumatoid arthritis Susceptible to TB [53,116–118]
$

Respective genes are known to escape from XCI

*

Transgenic IL-13 overexpressing C57BL/6 mice show necrosis and ↑ TB susceptibility

Abbreviations: CGD, Chronic granulomatous disease; MSMD, Mendelian susceptibility to mycobacterial disease; HCV, Hepatitis C virus; HIV-1, Human immunodeficiency virus −1; TLR, Toll like receptors; CYBB, Cytochrome B-245 Beta Chain; CD40L: CD40 ligand; IRAK1, Interleukin 1 receptor associated kinase 1; miR, MicroRNA PMN, Polymorphonuclear neutrophils, NEMO, Nuclear factor-κB (NF-κB) essential modulator; FOXP3, Forkhead box P3; IL13RA1 & RA2, Interleukin 13 receptor subunit alpha 1 and alpha 2; CXorf21, chromosome X open reading frame 21; SLC15A4, solute carrier family 15 member 4; SLE, Systemic Lupus Erythematosus. Upward arrow: increase; ss, single strand