Stromal cell and B cell dialog potentiates IL-33 enriched lymphoid niches to support eosinophil recruitment and function during type 2 immunity

Emily   Bessell; Rachel E. Finlay; Louisa K. James; Burkhard Ludewig; Nicola L. Harris; Philippe  Krebs; Matthew R. Hepworth; Lalit  Kumar Dubey

doi:10.1016/j.celrep.2024.114620

Stromal cell and B cell dialog potentiates IL-33 enriched lymphoid niches to support eosinophil recruitment and function during type 2 immunity

Emily Bessell, Rachel E. Finlay, Louisa K. James, Burkhard Ludewig, Nicola L. Harris, Philippe Krebs, Matthew R. Hepworth, Lalit Kumar Dubey

Research output: Contribution to journal › Article › peer-review

Abstract

Eosinophils are involved in host protection against multicellular organisms. However, their recruitment to the mesenteric lymph node (mLN) during type-2 immunity is understudied. Our results demonstrated that eosinophil association with lymphoid stromal niches constructed by FRCs and LECs, was diminished in mice selectively lacking IL-4Ra or LTβ expression on B cells. Furthermore, eosinophil survival, activation and enhanced Il1rl1 receptor expression was driven by stromal cell and B cell dialog. The ligation of LTβR on FRCs improved the eosinophil survival, significantly augmented the IL-33 expression and eosinophil homing to the mLN, thus confirming the significance of lymphotoxin signalling for granulocyte recruitment. Eosinophil-deficient ΔdblGATA-1 mice showed diminished mLN expansion, reduced IFR alarmin expression and delayed helminth clearance elucidating their importance in type-2 immunity. These findings provide insight into stromal cell and B cell dialog which govern mLN eosinophilia and relevance of these mechanisms during type-2 immunity.

Original language	English
Article number	114620
Journal	Cell Reports
Volume	43
Issue number	8
Early online date	13 Aug 2024
DOIs	https://doi.org/10.1016/j.celrep.2024.114620
Publication status	Published - 27 Aug 2024

Keywords

Eosinophils
IL-4Ra
Heligmosomoides polygyrus
Mesenteric lymph node
Fibroblastic Reticular Cells
Lymphatic endothelial cells
Stromal cells
IL-33
CCL24
B cell

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10.1016/j.celrep.2024.114620

Centre for Biological Timing
Lucas, R. (PI), Bechtold, D. (PI), Fustin, J.-M. (PI), Ashe, H. (PI), Brown, T. (PI), Blaikley, J. (PI), Brass, A. (PI), Chandola, T. (PI), Durrington, H. (PI), Else, K. (PI), Hepworth, M. (PI), Hunter, L. (PI), Kadler, K. (PI), Kitchen, G. (PI), Loudon, A. (PI), Macdonald, A. (PI), Mcbeth, J. (PI), Milosavljevic, N. (PI), Rattray, M. (PI), Rutter, M. (PI), Sharrocks, A. (PI), Spiller, D. (PI), Storchi, R. (PI), Belle, M. (PI), Meng, Q.-J. (PI), Allen, A. (PI), Dixon, W. (PI), Gibbs, J. (PI), Hazel, A. (PI), Papalopulu, N. (PI), Ray, D. (PI), White, M. (PI) & Chang, J. (PI)
Project: Research

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@article{f75a3a82a2ad428983521f297eaad0e0,

title = "Stromal cell and B cell dialog potentiates IL-33 enriched lymphoid niches to support eosinophil recruitment and function during type 2 immunity",

abstract = "Eosinophils are involved in host protection against multicellular organisms. However, their recruitment to the mesenteric lymph node (mLN) during type-2 immunity is understudied. Our results demonstrated that eosinophil association with lymphoid stromal niches constructed by FRCs and LECs, was diminished in mice selectively lacking IL-4Ra or LTβ expression on B cells. Furthermore, eosinophil survival, activation and enhanced Il1rl1 receptor expression was driven by stromal cell and B cell dialog. The ligation of LTβR on FRCs improved the eosinophil survival, significantly augmented the IL-33 expression and eosinophil homing to the mLN, thus confirming the significance of lymphotoxin signalling for granulocyte recruitment. Eosinophil-deficient ΔdblGATA-1 mice showed diminished mLN expansion, reduced IFR alarmin expression and delayed helminth clearance elucidating their importance in type-2 immunity. These findings provide insight into stromal cell and B cell dialog which govern mLN eosinophilia and relevance of these mechanisms during type-2 immunity.",

keywords = "Eosinophils, IL-4Ra, Heligmosomoides polygyrus, Mesenteric lymph node, Fibroblastic Reticular Cells, Lymphatic endothelial cells, Stromal cells, IL-33, CCL24, B cell",

author = "Emily Bessell and Finlay, {Rachel E.} and James, {Louisa K.} and Burkhard Ludewig and Harris, {Nicola L.} and Philippe Krebs and Hepworth, {Matthew R.} and {Kumar Dubey}, Lalit",

year = "2024",

month = aug,

day = "27",

doi = "10.1016/j.celrep.2024.114620",

language = "English",

volume = "43",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "8",

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TY - JOUR

T1 - Stromal cell and B cell dialog potentiates IL-33 enriched lymphoid niches to support eosinophil recruitment and function during type 2 immunity

AU - Bessell, Emily

AU - Finlay, Rachel E.

AU - James, Louisa K.

AU - Ludewig, Burkhard

AU - Harris, Nicola L.

AU - Krebs, Philippe

AU - Hepworth, Matthew R.

AU - Kumar Dubey, Lalit

PY - 2024/8/27

Y1 - 2024/8/27

N2 - Eosinophils are involved in host protection against multicellular organisms. However, their recruitment to the mesenteric lymph node (mLN) during type-2 immunity is understudied. Our results demonstrated that eosinophil association with lymphoid stromal niches constructed by FRCs and LECs, was diminished in mice selectively lacking IL-4Ra or LTβ expression on B cells. Furthermore, eosinophil survival, activation and enhanced Il1rl1 receptor expression was driven by stromal cell and B cell dialog. The ligation of LTβR on FRCs improved the eosinophil survival, significantly augmented the IL-33 expression and eosinophil homing to the mLN, thus confirming the significance of lymphotoxin signalling for granulocyte recruitment. Eosinophil-deficient ΔdblGATA-1 mice showed diminished mLN expansion, reduced IFR alarmin expression and delayed helminth clearance elucidating their importance in type-2 immunity. These findings provide insight into stromal cell and B cell dialog which govern mLN eosinophilia and relevance of these mechanisms during type-2 immunity.

AB - Eosinophils are involved in host protection against multicellular organisms. However, their recruitment to the mesenteric lymph node (mLN) during type-2 immunity is understudied. Our results demonstrated that eosinophil association with lymphoid stromal niches constructed by FRCs and LECs, was diminished in mice selectively lacking IL-4Ra or LTβ expression on B cells. Furthermore, eosinophil survival, activation and enhanced Il1rl1 receptor expression was driven by stromal cell and B cell dialog. The ligation of LTβR on FRCs improved the eosinophil survival, significantly augmented the IL-33 expression and eosinophil homing to the mLN, thus confirming the significance of lymphotoxin signalling for granulocyte recruitment. Eosinophil-deficient ΔdblGATA-1 mice showed diminished mLN expansion, reduced IFR alarmin expression and delayed helminth clearance elucidating their importance in type-2 immunity. These findings provide insight into stromal cell and B cell dialog which govern mLN eosinophilia and relevance of these mechanisms during type-2 immunity.

KW - Eosinophils

KW - IL-4Ra

KW - Heligmosomoides polygyrus

KW - Mesenteric lymph node

KW - Fibroblastic Reticular Cells

KW - Lymphatic endothelial cells

KW - Stromal cells

KW - IL-33

KW - CCL24

KW - B cell

U2 - 10.1016/j.celrep.2024.114620

DO - 10.1016/j.celrep.2024.114620

M3 - Article

SN - 2211-1247

VL - 43

JO - Cell Reports

JF - Cell Reports

IS - 8

M1 - 114620

ER -

Stromal cell and B cell dialog potentiates IL-33 enriched lymphoid niches to support eosinophil recruitment and function during type 2 immunity

Abstract

Keywords

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