RT Journal Article
SR Electronic
T1 Th2 single-cell heterogeneity and clonal interorgan distribution in helminth-infected mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.03.462935
DO 10.1101/2021.10.03.462935
A1 Daniel Radtke
A1 Natalie Thuma
A1 Philipp Kirchner
A1 Arif B Ekici
A1 David Voehringer
YR 2021
UL http://biorxiv.org/content/early/2021/10/03/2021.10.03.462935.abstract
AB Th2 cells provide effector functions in type 2 immune responses to helminths and allergens. Despite knowledge about molecular mechanisms of Th2 cell differentiation, there is little information on Th2 cell heterogeneity and clonal distribution between organs. To address this, we performed combined single-cell transcriptome and TCR clonotype analysis on murine Th2 cells in mesenteric lymph nodes (MLN) and lung after infection with Nippostrongylus brasiliensis (Nb) as a human hookworm infection model. We find organ-specific expression profiles, but also populations with conserved migration or effector/resident memory signatures that unexpectedly cluster with potentially regulatory Il10posFoxp3neg cells. A substantial MLN subpopulation with an interferon response signature suggests a role for interferon-signaling in Th2 differentiation or diversification. Further RNA-inferred developmental directions indicate proliferation as a hub for differentiation decisions. We also link long noted Cxcr3 expression in the Th2 compartment to a population of Il4pos NKT cells. Although the TCR repertoire is highly heterogeneous, we identified expanded clones and CDR3 motifs. Clonal relatedness between distant organs confirmed effective exchange of Th2 effector cells, although locally expanded clones dominated the response. These results provide new insights in Th2 cell subset diversity and clonal relatedness in distant organs.Competing Interest StatementThe authors have declared no competing interest.