We have demonstrated importance of elucidating futures of cells correlated with spatiotemporal information about cellular movement by using the mice expressing the photoconvertible protein Kaede and KikGR.
We reported that Foxp3+ regulatory T cells (Tregs) migrating from the skin to the draining lymph node have a strong immunosuppressive effect on contact hypersensitivity (CHS) response. To elucidate the role and characteristics of Treg subsets in CHS response in more details, we utilized a combination of single-cell real-time PCR high-dimensional gene expression profiling data with KikGR mice. We found that although immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs, Il10-expressing Tregs were rare and the majority of them co-expressed Gzmb and displayed Th1-skewing. Furthermore, Gzmb-/Il10-expressing Treg subset was gated with CD43+ CCR5+. In addition, CD43+CCR5+CXCR3- Tregs highly expressed skin-tropic chemokine receptors CCR4 and CCR8, preferred to retain within inflamed skin, and had superior in vivo inhibitory function. These results suggested that even if only present in small numbers, highly activated Tregs that co-express Gzmb and Il10 and that have the capacity to remain in inflamed tissue are likely to be clinically relevant due to the role of these molecules in the control of excessive immune responses. Taken together, the identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses.
In addition, requirement of elucidation of cellular movement between gut and another parts of body is increasing for revealing relation of gut immune system to systemic immune responses. Thus, I also introduce here that Tregs in caecum and ascending colon migrated to the distal part of mesenteric lymph node in an S1PR1-dependent manner in the steady state and dynamic changes of spatiotemporal regulation of colonic Tregs under inflammation.