IL-21 Promotes Intestinal Memory IgA Responses
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. I...
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Published in | The Journal of immunology (1950) Vol. 205; no. 7; pp. 1944 - 1952 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.10.2020
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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
, 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
compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal
-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
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. |
---|---|
AbstractList | The role of IL-21, produced mainly by T helper (Th) 17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and antibody 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 antigen-specific Th17 cells but not Th1 cells. Although IL-21R
−/−
mice or IL-17R
−/−
mice showed decreased antigen-specific memory IgA production in the intestines upon infection with
Citrobacter rodentium
(
C. rodentium
), the percentage of IgA
+
CD38
+
CD138
−
memory B cells in Peyer’s patches (PP) and LP was decreased only in IL-21R
−/−
mice, but not in IL-17R
−/−
mice, after re-infection with
C. rodentium
compared with WT mice. Blockade IL-21
in vivo
suppressed intestinal
C. rodentium
-specific IgA production as well as IgA
+
CD38
+
CD138
−
memory B cells in PP 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, Acida and Ski expression was decreased in B cells of IL-21R
−/−
mice after
C. rodentium
re-infection. In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development, possibly through up-regulating differentiation-related and class switching-related genes, indicating a potential role of IL-21 in memory IgA
+
B cell responses in the intestines. 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. 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 , 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 compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal -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 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 | Bilotta, Anthony J Cong, Yingzi Lu, Yao Kumar, Pawan Zhou, Zheng Dann, Sara M Yang, Wenjing Yao, Suxia Huang, Xiangsheng |
AuthorAffiliation | Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794 Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555 Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 |
AuthorAffiliation_xml | – name: Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794 – name: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 – name: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 – name: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555 |
Author_xml | – sequence: 1 givenname: Xiangsheng surname: Huang fullname: Huang, Xiangsheng organization: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 – sequence: 2 givenname: Wenjing orcidid: 0000-0003-1541-1892 surname: Yang fullname: Yang, Wenjing organization: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 – sequence: 3 givenname: Suxia surname: Yao fullname: Yao, Suxia organization: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 – sequence: 4 givenname: Anthony J surname: Bilotta fullname: Bilotta, Anthony J organization: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 – sequence: 5 givenname: Yao surname: Lu fullname: Lu, Yao organization: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 – sequence: 6 givenname: Zheng orcidid: 0000-0002-0390-9135 surname: Zhou fullname: Zhou, Zheng organization: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 – sequence: 7 givenname: Pawan surname: Kumar fullname: Kumar, Pawan organization: Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794 – sequence: 8 givenname: Sara M orcidid: 0000-0002-6893-2838 surname: Dann fullname: Dann, Sara M organization: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555; and – sequence: 9 givenname: Yingzi orcidid: 0000-0003-4167-7395 surname: Cong fullname: Cong, Yingzi email: yicong@utmb.edu organization: Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 |
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CitedBy_id | crossref_primary_10_1016_j_cyto_2022_156113 crossref_primary_10_1016_j_biopha_2023_114483 crossref_primary_10_1016_j_it_2021_06_003 crossref_primary_10_1186_s12943_024_02001_2 |
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Snippet | 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... 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... The role of IL-21, produced mainly by T helper (Th) 17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and... |
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SubjectTerms | Animals B-Lymphocytes - immunology Cells, Cultured Citrobacter rodentium - physiology Enterobacteriaceae Infections - immunology Immunoglobulin A - metabolism Immunoglobulin Class Switching - genetics Immunologic Memory Interleukins - metabolism Intestinal Mucosa - immunology Mice Mice, Inbred C57BL Mice, Knockout Receptors, Interleukin-21 - genetics Receptors, Interleukin-21 - metabolism Th17 Cells - immunology |
Title | IL-21 Promotes Intestinal Memory IgA Responses |
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