For quite a while the focus in IBD has revolved around Th1
and Th2 cell interactions. These cells have been widely implicated as being out
of balance, and one of the prime examples of immuno-dysregulation causing the
harmful disease IBD. Examples of this are abundant in previous papers regarding
this topic, but this week we will be taking a look at another player, the Th17
cell. The paper being discussed is this article published
in 2010, where the authors delve into the effector cytokines, genes involved in
differentiation, and recruitment of Th17 cells.
Please refer to the paper to see which interleukin’s and proteins
are involved in each category (located in the abstract) as I explain their
findings. This study aimed to clarify the involvement of Th17 in UC, CD, and
most importantly control groups. In order to quantify these concentrations and
asses involvement with each scenario, mRNA levels of each cytokine,
differentiation, or migration factor were evaluated by analyzing biopsies of inflamed
or healthy areas. PCR was used to amplify these findings.
The results of the collected mRNA discussed on page two
under the effector cytokines section had a couple of interesting results. IL17A
and IL22 were found to be highly expressed in all affected participants, except
in ileal CD where IL17A was weakly expressed, compared to the control. This
finding suggests that both IL17A and IL22 are very important in the
pathogenesis of IBD if they are so conserved. I believe more testing needs to
be conducted to discover what secretes each of these interleukins and how they
work, considering current research appears to be lacking on specifics. Another
interesting finding was that patients with UC located in the colon had higher
levels of IL17A and IL21 than patients with CD in the colon. IL21 is
responsible for activated NK and CTL cells, which I find curious. Why the need
to activate CTL cells, which deal with predominately viral problems, in a
bacterial area? This does, however, give support to the growing notion that CD
and UC are indeed separate diseases aside from affected locations.
In terms of the recruitment genes, CCR6 and CCL20, there
were also peculiar findings. It is important to understand that CCR6 is a
receptor for the CCL20 molecule as may be obvious the ‘R’ and ‘L’ present in
the respective abbreviations denoting receptor and ligand. CCR6 is attached to
dendritic cells along with a number of lymphocytes, including Th17 cells, but
needs more research. CCL20 is expressed
by inflamed tissues, including intestinal epithelia, and directs Th17 cells to
the site of inflammation. However, lower levels of CCR6 and CCL20 in ileal
samples suggest less Th17 involvement in this area. Why would there be a
greater need for Th17 in the colon? Unfortunately this area needs more research
to discern the reason for this behavior.
A few words of caution are raised in this article pertaining
to data collection. The first is that 42% of the affected patients were taking
anti-inflammatory medication at the time of sample collection. This gives rise
to the possibility of skewed cytokine expression, but the data was still
significant enough to be considered reliable information. The other concern was
in regards to using mRNA as a means to determine immunological function instead
of actual cytokine concentration but again, contributed to significant
findings.
An area of puzzlement in this paper was in its discussion of
the RORC gene. The paper refers to it as a master transcription factor with
specific isoforms for activated T cells, but I was having a lot of difficulty
in researching RORC’s function. If anyone is able to find information on this
it would be appreciated.
Overall this paper came to the conclusion that Th17 is
indeed highly involved in IBD, but the areas being affected, be it UC or CD,
offer variable expression. With these results it should be worth considering
different therapies or treatments should be pursued based on the location and
type of disease that has manifested. In my opinion, more work needs to be put
into discovering exact secretion and function of IL17A, IL22, and CCR6 to help
narrow down the root cause of IBD.
Sorry for the length, but I wanted to make up for a lack of
discussion time in class.
No comments:
Post a Comment