PMID- 35995508 OWN - NLM STAT- MEDLINE DCOM- 20220923 LR - 20230916 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 209 IP - 6 DP - 2022 Sep 15 TI - Migrating Type 2 Dendritic Cells Prime Mucosal Th17 Cells Specific to Small Intestinal Commensal Bacteria. PG - 1200-1211 LID - 10.4049/jimmunol.2200204 [doi] LID - ji2200204 AB - Dendritic cells (DCs) are professional APCs equipped with MHC-restricted Ags, costimulations, and cytokines that effectively prime and differentiate naive T cells into distinct functional subsets. The immune signals that DCs carry reflect the route of Ag uptake and the innate stimuli they received. In the mucosal tissues, owing to the great variety of foreign Ags and inflammatory cues, DCs are predominantly activated and migratory. In the small intestine, CD4 Th17 cells are abundant and have been shown to be regulated by DCs and macrophages. Using a mouse commensal bacteria experimental model, we identified that the early priming step of commensal-driven Th17 cells is controlled by bona fide Zbtb46-expressing DCs. CCR7-dependent migration of type 2 DCs (DC2s) from the small intestine to the mesenteric lymph nodes (MLNs) is essential for the activation of naive CD4 T cells. The migratory DC2 population in the MLNs is almost exclusively Esam(+) cells. Single-cell RNA sequencing highlighted the abundance of costimulatory markers (CD40 and OX40) and chemokines (Ccl22 and Cxcl16) on MLN migratory DCs. Further resolution of MLN migratory DC2s revealed that the Th17-polarizing cytokine IL-6 colocalizes with DC2s expressing CD40, Ccl17, and Ccl22. Thus, early Th17 cell differentiation is initiated by a small subset of migratory DC2s in the gut-draining lymph nodes. CI - Copyright (c) 2022 by The American Association of Immunologists, Inc. FAU - Ngoi, Soo AU - Ngoi S AD - Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH; and bei.liu@osumc.edu soomun.ngoi@osumc.edu. FAU - Yang, Yi AU - Yang Y AD - Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC. FAU - Iwanowycz, Stephen AU - Iwanowycz S AD - Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC. FAU - Gutierrez, Jennifer AU - Gutierrez J AD - Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC. FAU - Li, Yingqi AU - Li Y AD - Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC. FAU - Williams, Christina AU - Williams C AD - Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC. FAU - Hill, Megan AU - Hill M AD - Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH; and. FAU - Chung, Dongjun AU - Chung D AD - Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH; and. FAU - Allen, Carter AU - Allen C AD - Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH; and. FAU - Liu, Bei AU - Liu B AD - Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH; and bei.liu@osumc.edu soomun.ngoi@osumc.edu. LA - eng GR - R01 CA193939/CA/NCI NIH HHS/United States GR - U01 AI125859/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20220822 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - 0 (Receptors, CCR7) SB - IM MH - Bacteria MH - Chemokines MH - Cytokines MH - *Dendritic Cells MH - Interleukin-6 MH - Intestine, Small MH - Lymph Nodes MH - Mucous Membrane MH - Receptors, CCR7 MH - *Th17 Cells PMC - PMC9492644 MID - NIHMS1824349 COIS- COMPETING INTEREST STATEMENT The authors declare no competing interests EDAT- 2022/08/23 06:00 MHDA- 2022/09/24 06:00 PMCR- 2023/09/15 CRDT- 2022/08/22 21:04 PHST- 2022/03/18 00:00 [received] PHST- 2022/07/12 00:00 [accepted] PHST- 2022/08/23 06:00 [pubmed] PHST- 2022/09/24 06:00 [medline] PHST- 2022/08/22 21:04 [entrez] PHST- 2023/09/15 00:00 [pmc-release] AID - jimmunol.2200204 [pii] AID - 10.4049/jimmunol.2200204 [doi] PST - ppublish SO - J Immunol. 2022 Sep 15;209(6):1200-1211. doi: 10.4049/jimmunol.2200204. Epub 2022 Aug 22.