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2018 ; 9
(ä): 478
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Our Environment Shapes Us: The Importance of Environment and Sex Differences in
Regulation of Autoantibody Production
#MMPMID29662485
Edwards M
; Dai R
; Ahmed SA
Front Immunol
2018[]; 9
(ä): 478
PMID29662485
show ga
Consequential differences exist between the male and female immune systems'
ability to respond to pathogens, environmental insults or self-antigens, and
subsequent effects on immunoregulation. In general, females when compared with
their male counterparts, respond to pathogenic stimuli and vaccines more
robustly, with heightened production of antibodies, pro-inflammatory cytokines,
and chemokines. While the precise reasons for sex differences in immune response
to different stimuli are not yet well understood, females are more resistant to
infectious diseases and much more likely to develop autoimmune diseases.
Intrinsic (i.e., sex hormones, sex chromosomes, etc.) and extrinsic (microbiome
composition, external triggers, and immune modulators) factors appear to impact
the overall outcome of immune responses between sexes. Evidence suggests that
interactions between environmental contaminants [e.g., endocrine disrupting
chemicals (EDCs)] and host leukocytes affect the ability of the immune system to
mount a response to exogenous and endogenous insults, and/or return to normal
activity following clearance of the threat. Inherently, males and females have
differential immune response to external triggers. In this review, we describe
how environmental chemicals, including EDCs, may have sex differential influence
on the outcome of immune responses through alterations in epigenetic status (such
as modulation of microRNA expression, gene methylation, or histone modification
status), direct and indirect activation of the estrogen receptors to drive
hormonal effects, and differential modulation of microbial sensing and
composition of host microbiota. Taken together, an intriguing question develops
as to how an individual's environment directly and indirectly contributes to an
altered immune response, dysregulation of autoantibody production, and influence
autoimmune disease development. Few studies exist utilizing well-controlled
cohorts of both sexes to explore the sex differences in response to EDC exposure
and the effects on autoimmune disease development. Translational studies
incorporating multiple environmental factors in animal models of autoimmune
disease are necessary to determine the interrelationships that occur between
potential etiopathological factors. The presence or absence of autoantibodies is
not a reliable predictor of disease. Therefore, future studies should incorporate
all the susceptibility/influencing factors, coupled with individual genomics,
epigenomics, and proteomics, to develop a model that better predicts, diagnoses,
and treats autoimmune diseases in a personalized-medicine fashion.