Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology.

Masahito Kamanaka; Samuel Huber; Lauren A Zenewicz; Nicola Gagliani; Chozhavendan Rathinam; William O'Connor; Yisong Y Wan; Susumu Nakae; Yoichiro Iwakura; Liming Hao; Richard A Flavell

doi:10.1084/jem.20102149

Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology.

Standard

Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology. / Kamanaka, Masahito; Huber, Samuel; Zenewicz, Lauren A; Gagliani, Nicola; Rathinam, Chozhavendan; O'Connor, William; Wan, Yisong Y; Nakae, Susumu; Iwakura, Yoichiro; Hao, Liming; Flavell, Richard A.

In: J EXP MED, Vol. 208, No. 5, 5, 09.05.2011, p. 1027-1040.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kamanaka, M, Huber, S, Zenewicz, LA, Gagliani, N, Rathinam, C, O'Connor, W, Wan, YY, Nakae, S, Iwakura, Y, Hao, L & Flavell, RA 2011, 'Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology.', J EXP MED, vol. 208, no. 5, 5, pp. 1027-1040. https://doi.org/10.1084/jem.20102149

APA

Kamanaka, M., Huber, S., Zenewicz, L. A., Gagliani, N., Rathinam, C., O'Connor, W., Wan, Y. Y., Nakae, S., Iwakura, Y., Hao, L., & Flavell, R. A. (2011). Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology. J EXP MED, 208(5), 1027-1040. [5]. https://doi.org/10.1084/jem.20102149

Vancouver

Kamanaka M, Huber S, Zenewicz LA, Gagliani N, Rathinam C, O'Connor W et al. Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology. J EXP MED. 2011 May 9;208(5):1027-1040. 5. https://doi.org/10.1084/jem.20102149

Bibtex

@article{f32b9b86d99145ee8c532ba0b9b13a18,

title = "Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology.",

abstract = "The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10R?). We found that Foxp3-depleted CD45RB(lo) (regulatory T cell [T(reg) cell]-depleted CD45RB(lo)) but not CD45RB(hi) CD4(+) T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of T(reg) cell-depleted CD45RB(lo) CD4(+) T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RB(hi) T cells. In contrast to the CD45RB(hi) transfer colitis model, in which IL-22 is protective, we found that T cell-derived IL-22 was pathogenic upon transfer of T(reg) cell-depleted CD45RB(lo) T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RB(hi)) and memory/effector (T(reg) cell-depleted CD45RB(lo)) cells and different ways that IL-22 impacts inflammatory bowel disease.",

keywords = "Animals, Humans, Mice, Mice, Knockout, Antigens, CD45/genetics/*immunology/metabolism, Colitis/genetics/*immunology/metabolism/pathology, Colon/immunology/metabolism/pathology, Homeodomain Proteins/immunology/metabolism, *Immunologic Memory, Inflammatory Bowel Diseases/genetics/*immunology/metabolism/pathology, Interleukin-10/genetics/*immunology/metabolism, Interleukins/genetics/*immunology/metabolism, T-Lymphocytes, Regulatory/*immunology/metabolism/pathology, Th17 Cells/immunology/metabolism/pathology, Animals, Humans, Mice, Mice, Knockout, Antigens, CD45/genetics/*immunology/metabolism, Colitis/genetics/*immunology/metabolism/pathology, Colon/immunology/metabolism/pathology, Homeodomain Proteins/immunology/metabolism, *Immunologic Memory, Inflammatory Bowel Diseases/genetics/*immunology/metabolism/pathology, Interleukin-10/genetics/*immunology/metabolism, Interleukins/genetics/*immunology/metabolism, T-Lymphocytes, Regulatory/*immunology/metabolism/pathology, Th17 Cells/immunology/metabolism/pathology",

author = "Masahito Kamanaka and Samuel Huber and Zenewicz, {Lauren A} and Nicola Gagliani and Chozhavendan Rathinam and William O'Connor and Wan, {Yisong Y} and Susumu Nakae and Yoichiro Iwakura and Liming Hao and Flavell, {Richard A}",

year = "2011",

month = may,

day = "9",

doi = "10.1084/jem.20102149",

language = "English",

volume = "208",

pages = "1027--1040",

journal = "J EXP MED",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "5",

}

RIS

TY - JOUR

T1 - Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology.

AU - Kamanaka, Masahito

AU - Huber, Samuel

AU - Zenewicz, Lauren A

AU - Gagliani, Nicola

AU - Rathinam, Chozhavendan

AU - O'Connor, William

AU - Wan, Yisong Y

AU - Nakae, Susumu

AU - Iwakura, Yoichiro

AU - Hao, Liming

AU - Flavell, Richard A

PY - 2011/5/9

Y1 - 2011/5/9

N2 - The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10R?). We found that Foxp3-depleted CD45RB(lo) (regulatory T cell [T(reg) cell]-depleted CD45RB(lo)) but not CD45RB(hi) CD4(+) T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of T(reg) cell-depleted CD45RB(lo) CD4(+) T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RB(hi) T cells. In contrast to the CD45RB(hi) transfer colitis model, in which IL-22 is protective, we found that T cell-derived IL-22 was pathogenic upon transfer of T(reg) cell-depleted CD45RB(lo) T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RB(hi)) and memory/effector (T(reg) cell-depleted CD45RB(lo)) cells and different ways that IL-22 impacts inflammatory bowel disease.

AB - The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10R?). We found that Foxp3-depleted CD45RB(lo) (regulatory T cell [T(reg) cell]-depleted CD45RB(lo)) but not CD45RB(hi) CD4(+) T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of T(reg) cell-depleted CD45RB(lo) CD4(+) T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RB(hi) T cells. In contrast to the CD45RB(hi) transfer colitis model, in which IL-22 is protective, we found that T cell-derived IL-22 was pathogenic upon transfer of T(reg) cell-depleted CD45RB(lo) T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RB(hi)) and memory/effector (T(reg) cell-depleted CD45RB(lo)) cells and different ways that IL-22 impacts inflammatory bowel disease.

KW - Animals

KW - Humans

KW - Mice

KW - Mice, Knockout

KW - Antigens, CD45/genetics/immunology/metabolism

KW - Colitis/genetics/immunology/metabolism/pathology

KW - Colon/immunology/metabolism/pathology

KW - Homeodomain Proteins/immunology/metabolism

KW - Immunologic Memory

KW - Inflammatory Bowel Diseases/genetics/immunology/metabolism/pathology

KW - Interleukin-10/genetics/immunology/metabolism

KW - Interleukins/genetics/immunology/metabolism

KW - T-Lymphocytes, Regulatory/immunology/metabolism/pathology

KW - Th17 Cells/immunology/metabolism/pathology

KW - Animals

KW - Humans

KW - Mice

KW - Mice, Knockout

KW - Antigens, CD45/genetics/immunology/metabolism

KW - Colitis/genetics/immunology/metabolism/pathology

KW - Colon/immunology/metabolism/pathology

KW - Homeodomain Proteins/immunology/metabolism

KW - Immunologic Memory

KW - Inflammatory Bowel Diseases/genetics/immunology/metabolism/pathology

KW - Interleukin-10/genetics/immunology/metabolism

KW - Interleukins/genetics/immunology/metabolism

KW - T-Lymphocytes, Regulatory/immunology/metabolism/pathology

KW - Th17 Cells/immunology/metabolism/pathology

U2 - 10.1084/jem.20102149

DO - 10.1084/jem.20102149

M3 - SCORING: Journal article

C2 - 21518800

VL - 208

SP - 1027

EP - 1040

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 5

M1 - 5

ER -