Dataset Information

Coordinated co-migration of CCR10⁺ antibody-producing B cells with helper T cells for colonic homeostatic regulation.

ABSTRACT: In the intestine, IgA antibody-secreting B cells (IgA-ASCs) and helper T cells coordinate to maintain local homeostasis while their dysregulation could lead to development of intestinal inflammatory diseases. However, mechanisms underlying the coordinated localization and function of the B and T cells into the intestine, particularly the colon, are poorly understood. We herein report the first evidence that the gut-homing chemokine receptor CCR10⁺ IgA-ASCs form conjugates with helper T cells, preferentially regulatory T cells, at their differentiation sites of gut-associated lymphoid organs for their coordinated co-localization into the colon to promote local homeostasis. In CCR10-knockout mice, defective migration of IgA-ASCs also resulted in defective T-cell migration and homeostasis, and development of inflammatory symptoms in the colon. Antigen-specific interaction of CCR10⁺ IgA-ASCs and T cells is crucial for their homeostatic establishment in the colon. On the other hand, in IgA-knockout mice, preferential expansion of CCR10⁺ IgG1-ASCs with regulatory functions compensated for CCR10⁺ IgA-ASCs to help maintain colonic homeostasis. The preferential expansion of specific subclasses of CCR10⁺ IgG-ASCs with regulatory functions was also found in asymptomatic IgA-deficient patients. These findings suggest coordinated cell migration as a novel mechanism underlying localization and function of B and T cells in colonic homeostatic regulation.

SUBMITTER: Zhao L

PROVIDER: S-EPMC7870723 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Coordinated co-migration of CCR10<sup>+</sup> antibody-producing B cells with helper T cells for colonic homeostatic regulation.

Zhao Luming L Hu Shaomin S Davila Micha L ML Yang Jie J Lin Yang-Ding YD Albanese Joseph M JM Lo Yungtai Y Wang Yanhua Y Kennett Mary J MJ Liu Qiang Q Xiong Na N

Mucosal immunology 20200809 2

In the intestine, IgA antibody-secreting B cells (IgA-ASCs) and helper T cells coordinate to maintain local homeostasis while their dysregulation could lead to development of intestinal inflammatory diseases. However, mechanisms underlying the coordinated localization and function of the B and T cells into the intestine, particularly the colon, are poorly understood. We herein report the first evidence that the gut-homing chemokine receptor CCR10<sup>+</sup> IgA-ASCs form conjugates with helper ...[more]

PMID: 32773769

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Project description:BackgroundAging is the most important risk factor for prostate cancer (PCa), but how age contributes to PCa is poorly understood. Aging is characterized by low-grade systemic inflammation (i.e., inflammaging) that is often attributed to the progressive activation of immune cells over time, which may play an important role in prostate carcinogenesis. Th17 response is elevated in aging humans and mice, but it remains unknown whether it is increased in prostate tissue or contributes to prostate carcinogenesis during aging. In this study, we aimed to determine the role of age-related Th17 response in PCa cell growth, migration, and invasion.MethodsC57BL/6J (B6) mouse was used as an aging animal model and the prostate histopathology during aging was analyzed. Splenic CD4+ T cells were isolated from young (16-20 weeks old) and aged (96-104 weeks old) mice, and cultured in the presence of plate-bound anti-CD3/anti-CD28, with or without Th17 differentiation conditions. The cells were collected and used for subsequent flow cytometry or quantitative reverse transcription polymerase chain reaction. The supernatant was collected and used to treat PCa cell lines. The treated PCa cells were analyzed for cell viability, migration, invasion, and nuclear factor kappa B (NF-κB) signaling.ResultsAged mice had enlarged prostate glands and increased morphological alterations, with not only increased inflammatory cell infiltration but also increased Th17 cytokines in prostate tissue, compared to young mice. Naïve CD4+ T cells from aged mice differentiated increased interleukin (IL)-17-expressing cells. CD4+ T cells from aged mice spleen had increased Th17 cells, Th17 cytokines and Th17/Treg ratio compared to young mice. Factors secreted from aged CD4+ T cells, especially from ex vivo differentiated Th17 cells, not only promoted PCa cell viability, migration, and invasion but also activated the NF-κB signaling in PCa cells compared to young mice.ConclusionsThese results indicate that age-related CD4+ T cells, especially Th17 cells-secreted factors have the potential to contribute to prostate carcinogenesis. Our work could prompt further research using autochthonous PCa mouse models at different ages to elucidate the functional role of Th17 response in prostate carcinogenesis during aging.

Dataset Information

Coordinated co-migration of CCR10⁺ antibody-producing B cells with helper T cells for colonic homeostatic regulation.

Publications

Coordinated co-migration of CCR10<sup>+</sup> antibody-producing B cells with helper T cells for colonic homeostatic regulation.

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Dataset Information

Coordinated co-migration of CCR10+ antibody-producing B cells with helper T cells for colonic homeostatic regulation.

Publications

Coordinated co-migration of CCR10<sup>+</sup> antibody-producing B cells with helper T cells for colonic homeostatic regulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Coordinated co-migration of CCR10⁺ antibody-producing B cells with helper T cells for colonic homeostatic regulation.