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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2018-10, Vol.115 (42), p.E9849-E9858
• Main Authors: Obata-Ninomiya, Kazushige, Ishiwata, Kenji, Nakano, Hisanobu, Endo, Yusuke, Ichikawa, Tomomi, Onodera, Atsushi, Hirahara, Kiyoshi, Okamoto, Yoshitaka, Kanuka, Hirotaka, Nakayama, Toshinori
• Format: Article
• Language: English
• Subjects: Animals; Biological Sciences; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - parasitology; Fertility - immunology; Fertility - physiology; Immunologic Memory - immunology; Inflammation - immunology; Inflammation - metabolism; Inflammation - prevention & control; Interleukin-1 Receptor-Like 1 Protein - metabolism; Lung - immunology; Lung - metabolism; Lung - parasitology; Mice; Mice, Inbred BALB C; Myelin Basic Protein - metabolism; Nippostrongylus - immunology; PNAS Plus; Receptors, CXCR6 - metabolism; Receptors, Interleukin - metabolism; Strongylida Infections - complications; Strongylida Infections - parasitology; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1714731115

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.