IL-21 promotes intestinal memory IgA responses

Xiangsheng Huang; Wenjing Yang; Suxia Yao; Anthony J. Bilotta; Yao Lu; Zheng Zhou; Pawan Kumar; Sara M. Dann; Yingzi Cong

doi:10.4049/jimmunol.1900766

IL-21 promotes intestinal memory IgA responses

Xiangsheng Huang, Wenjing Yang, Suxia Yao, Anthony J. Bilotta, Yao Lu, Zheng Zhou, Pawan Kumar, Sara M. Dann, Yingzi Cong^*

^*Corresponding author for this work

Medicine, Gastroenterology Division

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

10 Scopus citations

Abstract

The role of IL-21, produced mainly by Th17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and Ab class switch. However, how IL-21 regulates memory IgA+ B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA+ B cells as well as CD38+CD138-IgA+ memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ-/- mice after transfer of microbiota Ag-specific Th17 cells but not Th1 cells. Although IL-21R-/- mice or IL-17R-/- mice showed decreased Ag-specific memory IgA production in the intestines upon infection with Citrobacter rodentium, the percentage of IgA+CD38+CD138- memory B cells in Peyer's patches and LP was decreased only in IL-21R-/- mice, but not in IL-17R-/- mice, after reinfection with C. rodentium compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal C. rodentium-specific IgA production as well as IgA+CD38+CD138- memory B cells in Peyer's patches and LP. Furthermore, IL-21 significantly induced B cell IgA production in vitro, with the increased expression of genes related with class-switching and memory B cell development, including Aicda, Ski, Bmi1, and Klf2. Consistently, Aicda and Ski expression was decreased in B cells of IL-21R-/- mice after C. rodentium reinfection. In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development, possibly through upregulating differentiation-related and class switching-related genes, indicating a potential role of IL-21 in memory IgA+ B cell responses in the intestines.

Original language	English (US)
Pages (from-to)	1944-1952
Number of pages	9
Journal	Journal of Immunology
Volume	205
Issue number	7
DOIs	https://doi.org/10.4049/jimmunol.1900766
State	Published - Oct 1 2020

Funding

This work was supported by National Institutes of Health Grants DK105585, DK112436, DK125011, AI150210 and DK124132, a Science and Technology Acquisition and Retention award from The University of Texas System (to Y.C.), and a McLaughlin postdoctoral fellowship from The University of Texas Medical Branch (to X.H.).

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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@article{93613a5efab0409aa5b2ff755ebd7afa,

title = "IL-21 promotes intestinal memory IgA responses",

abstract = "The role of IL-21, produced mainly by Th17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and Ab class switch. However, how IL-21 regulates memory IgA+ B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA+ B cells as well as CD38+CD138-IgA+ memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ-/- mice after transfer of microbiota Ag-specific Th17 cells but not Th1 cells. Although IL-21R-/- mice or IL-17R-/- mice showed decreased Ag-specific memory IgA production in the intestines upon infection with Citrobacter rodentium, the percentage of IgA+CD38+CD138- memory B cells in Peyer's patches and LP was decreased only in IL-21R-/- mice, but not in IL-17R-/- mice, after reinfection with C. rodentium compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal C. rodentium-specific IgA production as well as IgA+CD38+CD138- memory B cells in Peyer's patches and LP. Furthermore, IL-21 significantly induced B cell IgA production in vitro, with the increased expression of genes related with class-switching and memory B cell development, including Aicda, Ski, Bmi1, and Klf2. Consistently, Aicda and Ski expression was decreased in B cells of IL-21R-/- mice after C. rodentium reinfection. In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development, possibly through upregulating differentiation-related and class switching-related genes, indicating a potential role of IL-21 in memory IgA+ B cell responses in the intestines.",

author = "Xiangsheng Huang and Wenjing Yang and Suxia Yao and Bilotta, {Anthony J.} and Yao Lu and Zheng Zhou and Pawan Kumar and Dann, {Sara M.} and Yingzi Cong",

note = "Publisher Copyright: Copyright {\textcopyright} 2020 by The American Association of Immunologists, Inc.",

year = "2020",

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doi = "10.4049/jimmunol.1900766",

language = "English (US)",

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T1 - IL-21 promotes intestinal memory IgA responses

AU - Huang, Xiangsheng

AU - Yang, Wenjing

AU - Yao, Suxia

AU - Bilotta, Anthony J.

AU - Lu, Yao

AU - Zhou, Zheng

AU - Kumar, Pawan

AU - Dann, Sara M.

AU - Cong, Yingzi

PY - 2020/10/1

Y1 - 2020/10/1

N2 - The role of IL-21, produced mainly by Th17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and Ab class switch. However, how IL-21 regulates memory IgA+ B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA+ B cells as well as CD38+CD138-IgA+ memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ-/- mice after transfer of microbiota Ag-specific Th17 cells but not Th1 cells. Although IL-21R-/- mice or IL-17R-/- mice showed decreased Ag-specific memory IgA production in the intestines upon infection with Citrobacter rodentium, the percentage of IgA+CD38+CD138- memory B cells in Peyer's patches and LP was decreased only in IL-21R-/- mice, but not in IL-17R-/- mice, after reinfection with C. rodentium compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal C. rodentium-specific IgA production as well as IgA+CD38+CD138- memory B cells in Peyer's patches and LP. Furthermore, IL-21 significantly induced B cell IgA production in vitro, with the increased expression of genes related with class-switching and memory B cell development, including Aicda, Ski, Bmi1, and Klf2. Consistently, Aicda and Ski expression was decreased in B cells of IL-21R-/- mice after C. rodentium reinfection. In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development, possibly through upregulating differentiation-related and class switching-related genes, indicating a potential role of IL-21 in memory IgA+ B cell responses in the intestines.

AB - The role of IL-21, produced mainly by Th17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and Ab class switch. However, how IL-21 regulates memory IgA+ B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA+ B cells as well as CD38+CD138-IgA+ memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ-/- mice after transfer of microbiota Ag-specific Th17 cells but not Th1 cells. Although IL-21R-/- mice or IL-17R-/- mice showed decreased Ag-specific memory IgA production in the intestines upon infection with Citrobacter rodentium, the percentage of IgA+CD38+CD138- memory B cells in Peyer's patches and LP was decreased only in IL-21R-/- mice, but not in IL-17R-/- mice, after reinfection with C. rodentium compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal C. rodentium-specific IgA production as well as IgA+CD38+CD138- memory B cells in Peyer's patches and LP. Furthermore, IL-21 significantly induced B cell IgA production in vitro, with the increased expression of genes related with class-switching and memory B cell development, including Aicda, Ski, Bmi1, and Klf2. Consistently, Aicda and Ski expression was decreased in B cells of IL-21R-/- mice after C. rodentium reinfection. In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development, possibly through upregulating differentiation-related and class switching-related genes, indicating a potential role of IL-21 in memory IgA+ B cell responses in the intestines.

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EP - 1952

JO - Journal of Immunology

JF - Journal of Immunology

IS - 7

ER -

IL-21 promotes intestinal memory IgA responses

Abstract

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