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Cell DOI:10.1016/j.cell.2018.10.008

T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation.

Publication TypeJournal Article
Year of Publication2018
AuthorsBiton, M, Haber, AL, Rogel, N, Burgin, G, Beyaz, S, Schnell, A, Ashenberg, O, Su, C-W, Smillie, C, Shekhar, K, Chen, Z, Wu, C, Ordovas-Montanes, J, Alvarez, D, Herbst, RH, Zhang, M, Tirosh, I, Dionne, D, Nguyen, LT, Xifaras, ME, Shalek, AK, von Andrian, UH, Graham, DB, Rozenblatt-Rosen, O, Shi, HNing, Kuchroo, V, Yilmaz, ÖH, Regev, A, Xavier, RJ
Date Published2018 Nov 15

In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5 ISCs. We show that MHCII Lgr5 ISCs are non-conventional antigen-presenting cells in co-cultures with CD4 T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5 ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5 ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5 ISCs, thus, orchestrate tissue-wide responses to external signals.


Alternate JournalCell
PubMed ID30392957
PubMed Central IDPMC6239889
Grant ListP30 DK043351 / DK / NIDDK NIH HHS / United States
K99 AG045144 / AG / NIA NIH HHS / United States
RC2 DK114784 / DK / NIDDK NIH HHS / United States
R01 DK117263 / DK / NIDDK NIH HHS / United States
R00 AG045144 / AG / NIA NIH HHS / United States
R01 CA211184 / CA / NCI NIH HHS / United States
RM1 HG006193 / HG / NHGRI NIH HHS / United States