RORγt+ Innate Lymphoid Cells Protect Intestinal Flora

Editor’s note:

We’ve decided to alter the posting format to give you better research news coverage. Instead of a bi-weekly discussion of a single article, we will post news more often in a more abbreviated format. This decision is due to the huge number of relevant articles that are being published in the fields of inflammatory bowel disease and immunology. You can now expect posts every Tuesday. 

Functions of Innate Lymphoid CellsInnate lymphoid cells (ILCs) are the new “it” cells of the intestinal immune system. How they are activated and what they precisely do are hot research questions. Turns out that the activating receptor, NKp44, starts the pro-inflammatory engines of RORγt+ ILCs, and interestingly, these same cells also have an important role in protecting the intestinal microflora.

Activating RORγt+ ILCs with NKp44

New research presented in the Immunity article by Glatzer et al. shows that RORγt+ ILCs can be activated by the engagement of the activating receptor, NKp44 (in humans), which recognizes heparin sulfate and hyaluronic acid. This leads to the secretion of tumor necrosis factor (TNF) α, an extremely well-known pro-inflammatory cytokine. Normally, ILCs produce IL-22 when exposed to ambient cytokines. IL-22 is well-known for increasing intestinal barrier function. Most of the work was performed with ILCs isolated from human tonsils. ILCs isolated from mouse colon also released TNFα after activation, however, it was much less extreme.

RORγt+ ILCs and Microbiota Protection

Hepworth et al. in a letter to Nature described the ability of RORγt+ ILCs to protect intestinal flora from harmful CD4+ T cell response. Using a series of transgenic and knockout mice, they found that the loss of RORγt+ ILC caused an increase of abnormal flora-specific CD4+ T cell responses. This was mediated by RORγt+ ILC expression of MHC class II molecules. These molecules are normally used by antigen-presenting cells to stimulate CD4+ T cells. However, instead of increasing the proliferation of CD4+ T cells, it actually seemed to inhibit them. An experiment using animals with a mutated form of MHC class II on their ILCs showed that without this mechanism, the mice developed signs of inflammation in the colon.

Do you think that NKp44 activation plays a strong role in the colon? Let me know what you think!

References:

Glatzer, T., Killig, M., Meisig, J., Ommert, I., Luetke-Eversloh, M., Babic, M., et al. (2013). Innate Lymphoid Cells Acquirea Proinflammatory Program upon Engagement of the Activating Receptor NKp44. Immunity, 38(6), 1223–1235. doi:10.1016/j.immuni.2013.05.013

Hepworth, M. R., Monticelli, L. A., Fung, T. C., Ziegler, C. G. K., Grunberg, S., Sinha, R., et al. (2013). Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature, 498(7), 113–117. doi:10.1038/nature12240

 

 

 

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