Nasal administration of anti-CD3 mAb (Foralumab) downregulates NKG7 and increases TGFB1 and GIMAP7 expression in T cells in subjects with COVID-19
rho-Associated Kinases
SARS-CoV-2
T-Lymphocytes
Antibodies, Monoclonal
COVID-19
Membrane Proteins
Biological Sciences
3. Good health
Transforming Growth Factor beta1
Mice
GTP-Binding Proteins
Animals
Humans
Administration, Intranasal
DOI:
10.1073/pnas.2220272120
Publication Date:
2023-03-07T18:45:15Z
AUTHORS (14)
ABSTRACT
T cells are present in early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and play a major role in disease outcome and long-lasting immunity. Nasal administration of a fully human anti-CD3 monoclonal antibody (Foralumab) reduced lung inflammation as well as serum IL-6 and C-reactive protein in moderate cases of COVID-19. Using serum proteomics and RNA-sequencing, we investigated the immune changes in patients treated with nasal Foralumab. In a randomized trial, mild to moderate COVID-19 outpatients received nasal Foralumab (100 μg/d) given for 10 consecutive days and were compared to patients that did not receive Foralumab. We found that naïve-like T cells were increased in Foralumab-treated subjects and NGK7
+
effector T cells were reduced.
CCL5,
IL32,
CST7,
GZMH,
GZMB,
GZMA,
PRF1
, and
CCL4
gene expression were downregulated in T cells and
CASP1
was downregulated in T cells, monocytes, and B cells in subjects treated with Foralumab. In addition to the downregulation of effector features, an increase in
TGFB1
gene expression in cell types with known effector function was observed in Foralumab-treated subjects. We also found increased expression of GTP-binding gene
GIMAP7
in subjects treated with Foralumab. Rho/ROCK1, a downstream pathway of GTPases signaling was downregulated in Foralumab-treated individuals.
TGFB1,
GIMAP7
, and
NKG7
transcriptomic changes observed in Foralumab-treated COVID-19 subjects were also observed in healthy volunteers, MS subjects, and mice treated with nasal anti-CD3. Our findings demonstrate that nasal Foralumab modulates the inflammatory response in COVID-19 and provides a novel avenue to treat the disease.
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CITATIONS (11)
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