Does vitamin D cause atopy?
To the Editor,
Covid-19, caused by the severe acute respiratory syndrome coronavirus 2,
has brought threats to public health and has caused millions of deaths
to date. It is suggested that a cytokine storm in Covid-19 is associated
with greater mortality and clinical deterioration, attributing severe
cases to the increase of interleukin (IL) -1, tumor necrosis factor
(TNF) -ɑ, interferon (IFN) -γ and IL-6.1
Since the onset of the pandemic due Covid-19, evidence has indicated
that vitamin D (VD) deficiency is associated with a preeminent incidence
of infection2 and severity of Covid-19. As a
consequence, sales of vitamin supplements have increased during the
pandemic, including VD, due to its possible prophylactic or therapeutic
value.3
Prohormone and VD can be obtained from endogenous production prompted by
ultraviolet B radiation, from supplements, and from the diet. VD has
multiple regulatory effects in the human body (figure 1), since there is
evidence of the presence of its receptor in different
tissues.4 VD acts as a regulator of mineral
homeostasis considering its effects on parathyroids, bone and intestine
and has a variety of other biological functions, including
immunological.5
For this reason, it is possible to have effects on innate and adaptive
immunity, allowing the induction of monocyte and macrophage signaling,
especially on antimicrobial peptides such as cathelicidins and
β-defensin 2. Likewise, VD enables the inhibition of both B and T cells,
decreases IL-1, IL-6, TNF-ɑ and reduces antigen presenting cells such as
dendritic cells.5 Evidence highlights that vitamin D3
generates a shift from an inflammatory T-helper (Th) 1-cell response to
a pro-tolerogenic Th2 response with an arrest of cytotoxic T lymphocyte
infiltration and an increase in CD4+ CD25+ T regulatory cells
(Tregs).5 Hence, the possible development of atopy is
suspected in people who consume VD in excess.
Atopy refers to the disposition of developing an immune
hyperresponsiveness against allergens and antigens, leading to CD4+ Th2
polarization and immunoglobulin E (IgE)
overproduction.6 However, an increase in atopy has not
been seen due to the consumption of this vitamin.
Scrutinizing with the aforementioned, VD inhibits maturation,
differentiation, and survival of dendritic cells. It also down-regulates
major histocompatibility complex type II and costimulatory receptors
CD40, CD80 and CD865, which are elevated in
atopy7; hindering the interaction and activation of T
cells. Moreover, B cell proliferation and differentiation, even towards
IgE, is reduced.
Additionally, VD induces regulatory T-lymphocytes,5the latter being able to exhort immune tolerance by enhancing the
secretion of IL-10 and transforming growth factor β.7
The deterioration or absence of development of an allergic or atopic
disease by people who consume VD, can be explained by the action of
Tregs. The latter can subdue proliferation and activation of effector Th
cells, such as Th2 or Th17, and impede functions and migration of Th1,
thus IFN-γ, Th2, Th9 and Th17 cells.7 Responsively,
Th2 cytokines get suppressed8 by action of Tregs
during atopy, including mast cells, IgE, basophils, and
eosinophils,9 as shown in figure 2.
Tregs have suppressive mechanisms mediated by its inhibitory cytokines
and its stimulatory signals such as CTLA-4. This receptor implements an
immunoregulatory function, restraining T cell response by avoiding the
union of CD28 T-cell costimulatory molecule with its ligands CD80 and
CD86.
In conclusion, VD promotes immune homeostasis through Tregs, reducing
pro-inflammatory cytokines clustering, regulating levels of
anti-inflammatory cytokines and enhancing the production of
antimicrobial peptides. In this way, the derivation of an atopic disease
as a result of a supposed increase in Th2 lymphocytes is avoided due to
the consumption of this vitamin.