Intestinal inflammation alters the antigen-specific immune response to a skin commensal

A dynamic atlas of immunocyte migration from the gut

“…Extra-intestinal manifestations of inflammatory bowel disease are a good example of cell migration as a possible mechanism by which gut dysbiosis becomes a systemic problem. Migration of T cells from the intestines to the liver during colitis has been implicated in mediating liver pathogenesis 67 , and a recent report highlighted changes in the antigen-specificity of skin T cells following colitis 29 . Interestingly, the skin was one of very few tissues we could not detect any gut-derived immunocytes, thus implying that pathogenesis cannot be driven solely by corruption of existing axes of cell transport, but that new ones can form as a result of gut dysbiosis, or of local inflammation (as in the DTH ear).…”

“…Kaede transgenic mice express a fluorescent protein that converts from green to red upon exposure to violet light, making them an ideal tool to in vivo track cellular migration minimally invasively 25 . They have been previously used to temporally trace the migration of intestinal cells following photoconversion of the small intestine or ascending colon via surgical exposure 19,[26][27][28][29] , or in combination with a less invasive endoscopic system 14,16 . While it was shown that immunocytes can exit the intestines, information on their destination and function has primarily concerned lymphoid tissues (mostly local LNs), or specific cell types in autoimmune models 14,15,18,19,30,31 .…”

Early life tolerance depends on a subset of specialized dendritic cells and is reinforced by the skin microbiota

“…Some additional markers, e.g. OX40L (Merana et al, 2022), were additionally found to be increased in S. epi- zsgreen-containing CD301b + DC2 at the protein but not mRNA level (Fig. 5C.…”

“…Next, we examined the relative capacity of DC2 versus other subsets to present commensal antigen and induce antigen-specific CD4 + T cell proliferation. For this we engineered a strain of S. epidermidis to express the CD4 + epitope of ovalbumin (OVA), recognized by OT-II T cells ( S. epi- OVA) (Merana et al, 2022). To test the capacity for antigen presentation independently from uptake, we sorted CD11b hi DC2, CD11b lo DC2, DC1 and LC from the migDC population of neonatal SDLN prior to directly incubating ex vivo overnight with S. epi- OVA (Fig.…”

“…epi-OVA) (Merana et al, 2022).To test the capacity for antigen presentation independently from uptake, we sorted CD11b hi DC2, CD11b lo DC2, DC1 and LC from the migDC population of neonatal SDLN prior to directly incubating ex vivo overnight with S. epi-OVA (Fig. 3H).…”