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Journal of Timely Topics in Clinical Immunology | Volume 2
July 26-28, 2018 | Moscow, Russia
Immunology
11
th
Annual Congress on
Class IV semaphorin checkpoints regulate allergic asthma
Svetlana P Chapoval
University of Maryland, USA
T
wo class IV semaphorins, Sema4A and Sema4D, belong to a
family of neuron guidance proteins which were also found
to be expressed and function in the immune system. They
both act as immune checkpoints by either directly or indirectly
regulating T cell activation. We defined the in vivo function
of Sema4 molecules in allergic asthma using OVA challenges
of corresponding semaphorin-deficient mice. We found that
Sema4A and 4D molecules play the opposite roles in disease.
Whereas Sema4A-/- mice demonstrated a selective increase
in airway eosinophilia accompanied by bronchial epithelial cell
hyperplasia as compared toWTmice, these asthma parameters
weredecreased inSema4D-/-mice. Theenhanced inflammatory
response in Sema4A-/- mice was associated with a selective
increase in bronchoalveolar lavage IL-13 content, augmented
airway hyperreactivity (AHR), and lower Treg cell numbers. In
contrast, lower Th2 cytokine levels and higher number of Treg
cells were found in the lungs of Sema4D-/- mice, whereas AHR
was not affected. Allergen-primed Sema4A-/- CD4+ T cells
were more effective in transferring Th2 response to naive mice
as compared with WT CD4+ T cells. T-cell proliferation and IL-
13 productions were upregulated in OVA₃₂₃₋₃₃₉-restimulated
Sema4A-/- cell cultures and downregulated in Sema4D-/-
cultures as compared to similarly challenged WT cells.
Generatedbonemarrowchimeras showedanequal importance
of both lung-resident cell and inflammatory cell Sema4A
expression in optimal disease regulation. These data provide a
new insight into Sema4 biology and define Sema4 molecules
as important regulators of Th2-driven lung pathophysiology
and prospective targets for disease immunotherapy.
e:
SChapoval@som.umaryland.edu