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Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9849-E9858. doi: 10.1073/pnas.1714731115. Epub 2018 Oct 1.

CXCR6+ST2+ memory T helper 2 cells induced the expression of major basic protein in eosinophils to reduce the fecundity of helminth.

Author information

1
Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, 260-8670 Chiba, Japan.
2
Department of Tropical Medicine, The Jikei University School of Medicine, 105-8461 Tokyo, Japan.
3
Department of Immunology, Graduate School of Medicine, Chiba University, 260-8670 Chiba, Japan.
4
Institute for Global Prominent Research, Chiba University, 263-8522 Chiba, Japan.
5
Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 260-8670 Chiba, Japan.
6
Department of Immunology, Graduate School of Medicine, Chiba University, 260-8670 Chiba, Japan; tnakayama@faculty.chiba-u.jp.

Abstract

Memory T helper (mTh) cells play important roles in the reinfection of pathogens and drive the pathogenesis of diseases. While recent studies have characterized the pathogenic mTh2 cell subpopulations driving allergic inflammation, those that induce immune responses against helminth infection remain unknown. We found that IL-5-producing CXCR6+ST2+CD44+ mTh2 cells play a crucial role in the IL-33-dependent inhibition of the fecundity of helminth, whereas other ST2- mTh2 cells do not. Although both cell types induced the infiltration of granulocytes, especially eosinophils, into the lungs in response to helminth infection, the ST2+ mTh2 cell-induced eosinophils expressed higher levels of major basic protein (MBP), which is important for reducing the fecundity of Nippostrongylus brasiliensis (Nb), than ST2- mTh2 cell-induced ones. Notably, we also found that ST2+ Treg cells but not ST2- Treg cells suppressed CXCR6+ST2+ mTh2 cell-mediated immune responses. Taken together, these findings show that we identified a mechanism against helminth elicited by a subpopulation of IL-5-producing mTh2 cells through the accumulation of eosinophils strongly expressing MBP in the lungs.

KEYWORDS:

IL-33/ST2; Treg; allergic inflammation; helminth; memory Th2 cell subset

PMID:
30275296
PMCID:
PMC6196506
DOI:
10.1073/pnas.1714731115
[Indexed for MEDLINE]
Free PMC Article

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