Effects beyond the late phase
The detected amounts of IL-8, IL-13 and LIF are still significantly
different from baseline 24 hours after allergen activation (p
< 0.001) (figure 2, a-c). This could indicate an effect of
these cytokines that goes beyond the late phase response (6-8 hours) and
possibly adds to the development of chronic inflammation. Increased
cytokine secretion may be associated with asthma severity as is
supported by studies showing higher levels of IL-8 and IL-13 in patients
with chronic severe asthmatic disease in addition to a negative
correlation of cytokine secretion with lung function (20,30,31) .
Several cytokines novel to the mast cell were also significantly
upregulated by high affinity IgE (CSF-1, FLT3L, HGF, OSM and IL-12b).
CSF-1 and Flt3L may be involved in maintenance and activation of
hematopoietic progenitors, and HGF supports angiogenesis and tissue
regeneration of epithelial cells. OSM remains poorly defined, but
closely related to IL-6 and LIF.
When combining the current results with data from animal models(1,2)
mast cells seem to be able to sense differences in IgE affinity and this
may have important implications for their role in shaping early and late
phase allergic responses and may even impact chronic asthma by bridging
between different endotypes dominated by immune cell subsets favored by
different mast cell mediators. Clearly, additional experiments are
needed to substantiate the direct effects of molecular editing through
kinetic proofreading in human as well as mouse mast cells and its
downstream effects. Moreover, links between IgE affinity and asthma
endotypes may be followed up in allergic individuals with primarily high
vs low affinity IgE towards well characterized allergens.