Citations 2
The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4 + eosinophils unique to the small intestine
Wang, Wei-Le , Kasamatsu, Jun , Gilfillan, Susan , Luccia, Blanda Di , Panda, Santosh K., Kim, DoHyun , Desai, Pritesh , Bando, Jennifer K. , Yomogida, Kentaro , Hoshino, Hitomi , Fukushima, Mana, Jacobsen, Elizabeth A. , Dyken, Steven J. Van , Ruedl, Christiane , Gilfillan, Susan , Bando, Jennifer K , Van Dyken, Steven J , Ruedl, Christiane , Colonna, Marco , Jacobsen, Elizabeth A , Joshita, Satoru , Panda, Santosh K., Huang, Stanley Ching‐Cheng , Cella, Marina , Colonna, Marco
Proceedings of the National Academy of Sciences | June 2, 2022 | Volume: 119 | Issue: 23 | Pages: No page available
Significance Eosinophils contribute to type 2 immunity against helminths and allergens. The small intestine harbors eosinophils with incompletely understood pathophysiological roles. Here, we show that intestinal eosinophils include two subsets. One expresses the inhibitory receptor Clec4a4 and the inhibitory ligand PD-L1 and is unique to the small intestine; the other manifests a proinflammatory phenotype. Both subsets are blood derived. Remarkably, Clec4a4 + eosinophils were instructed by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that imprints many gut immune cells. Selective AHR deletion in eosinophils depleted Clec4a4 + eosinophils, augmented innate lymphocytes producing type 2 cytokines, and enhanced helminth clearance. We conclude that Clec4a4 + eosinophils have immunomodulatory functions, which could be harnessed for the therapy of food allergies and eosinophilic gastrointestinal disorders.
Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders
Brioschi, Simone , Wang, Wei-Le , Peng, Vincent , Wang, Meng , Shchukina, Irina, Greenberg, Zev J. , Bando, Jennifer K. , Jaeger, Natália , Czepielewski, Rafael S. , Swain, Amanda , Mogilenko, Denis A. , Beatty, Wandy L. , Fitzpatrick, James A. J. , Schuettpelz, Laura G. , Fronick, Catrina C. , Smirnov, Igor , Kipnis, Jonathan , Wu, Gregory F. , Gilfillan, Susan , Artyomov, Maxim N. , Fitzpatrick, James A J , Fronick, Catrina C , Kipnis, Jonathan , Shapiro, Virginia S , Wu, Gregory F , Gilfillan, Susan , Cella, Marina , Artyomov, Maxim N , Kleinstein, Steven H , Colonna, Marco , Bando, Jennifer K , Brioschi, Simone , Bayguinov, Peter O. , Shapiro, Virginia Smith , Colonna, Marco
Science | June 3, 2021 | Volume: 373 | Issue: 6553 | Pages: No page available
Getting around the blood–brain barrier The meninges comprise three membranes that surround and protect the central nervous system (CNS). Recent studies have noted the existence of myeloid cells resident there, but little is known about their ontogeny and function, and whether other meningeal immune cell populations have important roles remains unclear (see the Perspective by Nguyen and Kubes). Cugurra et al. found in mice that a large proportion of continuously replenished myeloid cells in the dura mater are not blood derived, but rather transit from cranial bone marrow through specialized channels. In models of CNS injury and neuroinflammation, the authors demonstrated that these myeloid cells have an immunoregulatory phenotype compared with their more inflammatory blood-derived counterparts. Similarly, Brioschi et al. show that the meninges host B cells that are also derived from skull bone marrow, mature locally, and likely acquire a tolerogenic phenotype. They further found that the brains of aging mice are infiltrated by a second population of age-associated B cells, which come from the periphery and may differentiate into autoantibody-secreting plasma cells after encountering CNS antigens. Together, these two studies may inform future treatment of neurological diseases. Science , abf7844, abf9277, this issue p. eabf7844 , p. eabf9277 ; see also abj8183, p. 396