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

Luming Zhao, Shaomin Hu, Micha L. Davila, Jie Yang, Yang Ding Lin, Joseph M. Albanese, Yungtai Lo, Yanhua Wang, Mary J. Kennett, Qiang Liu, Na Xiong

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalMucosal Immunology
DOIs
StateAccepted/In press - 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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