Panicle-Shaped Sympathetic Architecture in the Spleen Parenchyma Modulates Antibacterial Innate Immunity

Ding, Xiaofan; Wang, Huanhuan; Qian, Xinmin; Han, Xiangli; Yang, Lu; Cao, Ying; Wang, Qi; Yang, Jing

doi:10.1016/j.celrep.2019.05.082

Cited by 45 publications

(37 citation statements)

References 37 publications

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“…8c). This is in contrast with longstanding dogma 39 as well as a recent 3D imaging study of cleared SPL from mice where ChAT + nerve fibers were not detected 40 . Renderings of sequential optical slices through the Z dimension (~1000-2000)…”

Section: D-imaging Of Perivascular Innervation In Spl and Lncontrasting

confidence: 85%

Immune, endothelial and neuronal network map in human lymph node and spleen

Currlin

Nick

Jorgensen

et al. 2021

Preprint

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As secondary lymphoid organs, the spleen and lymph node represent important hubs for both innate and adaptive immunity. Neuroanatomical and tracing data, largely derived from rodents, suggest that lymph nodes contain sensory and sympathetic innervation, whereas the spleen contains postganglionic sympathetic innervation, with conflicting views regarding the existence of cholinergic or vagal innervation. Herein, we map the neuronal, vascular, and sinus cell networks from human spleen and lymph node using highly multiplexed CODEX (CO-Detection by indEXing) and 3D light sheet microscopy of cleared tissues. These data demonstrate striking delineation of two distinct layers within the lymph node subcapsular sinus-the ceiling defined by Podoplanin expression and floor by LYVE1, which overlays the lymph node follicles. Within the lymph node interior, we observed a mesh-like vessel network innervated with GAP43 and beta3-tubulin. Dense perivascular innervation occurred in both tissues, including a subset of axonal processes expressing choline acetyl transferase (ChAT). Four neuronal markers (ChAT, PGP9.5, tyrosine hydroxylase, and beta3-tubulin) localized to the arterial tunica externa suggest expression in the nervi vasorum while GAP43 was expressed within the internal elastic membrane of arteries. These data represent highly novel 3D visualization of perivascular and periductal autonomic innervation within these two key human organs.

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Section: D-imaging Of Perivascular Innervation In Spl and Lncontrasting

confidence: 85%

Immune, endothelial and neuronal network map in human lymph node and spleen

Currlin

Nick

Jorgensen

et al. 2021

Preprint

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“…Recent studies have revealed an intricate, panicle-shaped sympathetic architecture in the spleen (126). Most detectable nerves entering the spleen arise from the nerve plexus that surrounds branches of the splenic artery and are catecholaminergic (127).…”

Section: The Nervous System and Neural Signal-expressing Cellsmentioning

confidence: 99%

Generation of Myeloid Cells in Cancer: The Spleen Matters

Hua

Zheng

2020

Front. Immunol.

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Myeloid cells are key components of the tumor microenvironment and critical regulators of disease progression. These innate immune cells are usually short-lived and require constant replenishment. Emerging evidence indicates that tumors alter the host hematopoietic system and induce the biased differentiation of myeloid cells to tip the balance of the systemic immune activities toward tumor-promoting functions. Altered myelopoiesis is not restricted to the bone marrow and also occurs in extramedullary organs. In this review, we outline the recent advances in the field of cancer-associated myelopoiesis, with a focus on the spleen, the major site of extramedullary hematopoiesis in the cancer setting. We discuss the functional specialization, distinct mechanisms, and clinical relevance of cancer-associated myeloid cell generation from early progenitors in the spleen and its potential as a novel therapeutic target.

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“…In contrast, after 6-OHDA administration, the absolute cell counts and percentages of CD3 − NK1.1 + and the absolute cell counts of CD3 + NK1.1 + were increased in the spleen. The splenic parenchyma is rich in sympathetic innervation expressing both synaptophysin and tyrosine hydroxylase, displaying a unique, complex, and panicle-like neuronal architecture ( 23 ). Qi et al.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Immune Responses of Peripheral Chemical Sympathectomy in Enterovirus 71 Infection

et al. 2021

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The activation of the sympathetic nervous system, release of norepinephrine (NE), and adrenergic receptor signaling participate in and regulate the complicated enterovirus 71 (EV71) brainstem encephalitis (BE). The neurotoxin 6-hydroxydopamine (6-OHDA) selectively ablates sympathetic nerves and markedly depletes NE in innervated organs. Changes in the plasma levels of NE, severity score, cytokine profiles, and percentages of immunophenotype expression in 7-day-old Bltw : CD1 (ICR) mice infected with EV71, with or without 6-OHDA treatment, were compared. The survival rate (76.9%) of EV71-infected and 6-OHDA (30 μg/g)-treated mice was increased significantly. The clinical scores were decreased markedly on days 8-12 in MP4-infected and 6-OHDA-treated mice compared to those without treatment. The results showed that the plasma levels of NE, epinephrine, and dopamine were decreased on days 4–8 after 6-OHDA treatment and at most on day 8. The plasma levels of interleukin (IL)-12p70, tumor necrosis factor, IL-6, and IL-10 did not change significantly after 6-OHDA treatment. Interferon-γ levels decreased evidently on days 4, 6, and 8 after 6-OHDA treatment. The absolute events of CD3+CD4+, CD3+CD8+, and CD3+NK1.1+ cells of peripheral blood mononuclear cells were increased significantly in MP4-infected and 6-OHDA-treated mice compared to those without treatment. In splenocytes, the absolute cells of CD3−NK1.1+, CD3+NK1.1+ and CD11b+Gr-1+ cells of EV71-infected mice were increased significantly after 6-OHDA treatment. These findings suggested that 6-OHDA may be used a probe to explore clinical improvements and immune responses in the complicated EV71 infection. Taken together, peripheral chemical sympathectomy contribute to further understand the immunopathogenesis of EV71 BE with autonomic nervous system dysregulation.

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Panicle-Shaped Sympathetic Architecture in the Spleen Parenchyma Modulates Antibacterial Innate Immunity

Cited by 45 publications

References 37 publications

Immune, endothelial and neuronal network map in human lymph node and spleen

Immune, endothelial and neuronal network map in human lymph node and spleen

Generation of Myeloid Cells in Cancer: The Spleen Matters

Clinical and Immune Responses of Peripheral Chemical Sympathectomy in Enterovirus 71 Infection

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