Page 287 - Veterinary Immunology, 10th Edition
P. 287
On the other hand, inflammatory mediators, such as IL-10,
VetBooks.ir transforming growth factor-α (TGF-α), prostaglandin E (PGE ),
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histamine, extracts of parasitic worms, or the toxin of Vibrio cholerae,
promote cDC2 production. cDC2 responses may also be triggered
by bacterial lipopolysaccharides and proteoglycans acting through
TLR2, TLR6, or TLR1. Ligands of TLR2 promote the production of
IL-23 and thus promote Th17 cell responses. As pointed out
previously, a similar functional subdivision occurs in macrophages.
Thus M1 and M2 cells, when acting as antigen-presenting cells, also
promote different helper cell responses.
It may also be that the same dendritic cell can promote a type 1,
type 2, or Th17 response, depending on the dose and type of
antigen it encounters. The response may also depend on its
location. For example, DCs from the intestine or airways seem to
preferentially secrete IL-10 and IL-4 and thus promote type 2
responses. In such cases, the intestinal microbiota may provide the
cDC2–polarizing signals.
pDCs increase dramatically during inflammation and infection.
They are relatively inefficient in promoting helper cell proliferation
but produce large quantities of IFN-γ and IL-17. They thus promote
Th1 polarization.
Interleukin-12
IL-12 is a key cytokine produced by macrophages, DCs, B cells, and
neutrophils. Its targets are T cells and NK cells. IL-12 determines
Th1/Th2 polarization. Th1 cells develop when it is present. Th2 cells
develop when it is absent. IL-12 is a member of a family of related
proteins that also includes IL-23, IL-27, IL-35 and IL-39. These are
all heterodimeric proteins. For example, IL-12 is formed by two
chains, p35 and p40. Some of these chains are shared with other
family members. All the members of the family regulate T cell
function. Thus IL-12 and IL-27 generate Th1 cells, whereas IL-23
generates Th17 cells.
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