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.
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Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers AR064831 and Pennsylvania State University institutional support (to N.X.) and Montefiore Medical Center Pathology Research Funding (to S.H.). The content is solely the responsibility of the authors and does not necessarily represent official views of the funding agencies. We thank the Clinical Immunology lab of Montefiore Medical Center for excellent technical support for IHC staining.
The authors declare no competing interests.
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Zhao, L., Hu, S., Davila, M.L. et al. Coordinated co-migration of CCR10+ antibody-producing B cells with helper T cells for colonic homeostatic regulation. Mucosal Immunol 14, 420–430 (2021). https://doi.org/10.1038/s41385-020-0333-3