Dear Xin, 

we found a rather protective function of IL-17A in our 2016 Mucosal Immunology paper and other people have described this, too.

For the IFNg, you are absolutely right: The contribution of different sources of IFNg remains unclear: We found that IFNg-deficient T cells induced very potent disease that was only mildly reduced compared to WT. However, when we administered an anti-IFNg blocking antibody thus neutralizing IFNg not only from the T cells but from all cells, colitis was prevented altogether. Therefore it seems that the T cell-derived IFNg is not critical in this model but IFNg in general is.

The main message of our paper was that indeed Th1 cells are not critical for colitis as we get strong colitis induction also with T-bet-deficient T cells – an observation that also Krausgruber & Schiering et al have published last year. This seems to be at odds with the report from Neurath and colleagues in 2002 that described Th1 cells to be critical. We have just published this year that it is indeed the microbiota composition of the recipient that determines the requirement for Th1 cells: In one cohort of Rag-/- mice, T-bet-deficient Th cells could not induce colitis, just as published originally. When we colonise these mice with a different microbiota they become susceptible for colitis induction by T-bet-deficient Th cells.

Dear Xin Wang,

To my knowledge, CD4 cells are integral part of induction, maintenance and progression of colitis....administration of Anti-CD4 antibodies will produce rapid remission in clinical signs of colitis....please go through the enclosed articles than will be useful...

Please go through the attached article....hope it will be useful...

Dear Xin,

there are colitis models where inflammation develops independently of adaptive lymphocytes such as the anti-CD40 model or even DSS colitis which also works in Rag ko mice.

Concerning which T cell subset is responsible for the inflammation, there is still much debate ongoing. In the T cell transfer model referenced by Selvam, early reports have found that Th1 cells are critical while we and others showed recently that they are not. Similar controversial results have been obtained for Th17 cells: It is clear that IL-23 plays a pathogenic role in this model and also Rorc-deficient T cells seem to be impaired in inducing inflammation. However, at least in our hands, the signature cytokine IL-17A had a protective rather than a pro-inflammatory function in T cell transfer colitis. What is generally becoming more and more clear now is that the required pathomechanisms seem to depend strongly on the microbiota composition of the host.

For more details have a look at one of the numerous review articles out there.

Hi Jakob,

Which publication can prove that ' the signature cytokine IL-17A had a protective rather than a pro-inflammatory function in T cell transfer colitis'.

I have one more question, about the for IFNg, there are many cells that can secret the IFNg, so the increase of IFNg (gene expression/ protein level) in the colon tissue doesn't mean the increase of Th1 cells right ? so Th1 cells may not be the pathgenic factor in colitis?

Xin 

Dear Xin, 

we found a rather protective function of IL-17A in our 2016 Mucosal Immunology paper and other people have described this, too.

For the IFNg, you are absolutely right: The contribution of different sources of IFNg remains unclear: We found that IFNg-deficient T cells induced very potent disease that was only mildly reduced compared to WT. However, when we administered an anti-IFNg blocking antibody thus neutralizing IFNg not only from the T cells but from all cells, colitis was prevented altogether. Therefore it seems that the T cell-derived IFNg is not critical in this model but IFNg in general is.

The main message of our paper was that indeed Th1 cells are not critical for colitis as we get strong colitis induction also with T-bet-deficient T cells – an observation that also Krausgruber & Schiering et al have published last year. This seems to be at odds with the report from Neurath and colleagues in 2002 that described Th1 cells to be critical. We have just published this year that it is indeed the microbiota composition of the recipient that determines the requirement for Th1 cells: In one cohort of Rag-/- mice, T-bet-deficient Th cells could not induce colitis, just as published originally. When we colonise these mice with a different microbiota they become susceptible for colitis induction by T-bet-deficient Th cells.

Hi Jakob,

    Thank you for your detailed information! you really helped me a lot about this question. I

    Here I can not get access to your publicaiton, could you please send me this publication 'The intestinal microbiota determines the colitis-inducing potential of T-bet-deficient Th cells in mice'  Thanks!

Xin

Fully agree with all that Jakob said here. In my opinion, the field is moving to better understand the interplay between the different (and some quite plastic) T cell "lineages" or phenotypes and the microbiota/other host conditions in each colitis model. These 2 recent papers also shed light into the discussion, supporting the idea that it is not just one unique type of T cell that drives or perpetuates pathogenicity, but a combination of different types of T cells and host factors.

http://www.pnas.org/content/112/22/7061.abstract

http://www.jimmunol.org/content/196/12/4893

There are several other colitis models where T cells are more or less dispensable, but it all depends strongly on the colitis model. Other such models to consider where both innate and adaptive immune systems play a big role are e.g. the IL-10 deficient mice: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511684/

Best, 

Damian