AI Article Synopsis

  • Asthma is driven by Th2-type inflammation, and the transcription factor LZTFL1 plays a crucial role in regulating Th2-related factors, impacting levels of cytokines like IL-4, IL-5, and IL-13.
  • In a mouse model of acute asthma induced by Ovalbumin, knocking down LZTFL1 led to reduced symptoms (sneezing and nose rubbing), diminished inflammatory cell infiltration, and lower levels of OVA-specific IgE and pro-inflammatory cytokines.
  • LZTFL1 knockdown also interfered with the MEK/ERK signaling pathway, reduced the number of GATA3+ CD4+ Th2 cells, and showed that LZTFL1 may modulate

Article Abstract

Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 10 TU of lentivirus via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced inflammatory cell infiltration, reduced goblet cell numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding protein 3 (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway.

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Source
http://dx.doi.org/10.1016/j.molimm.2024.01.010DOI Listing

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