The discovery of a new type of innervation in lymphoid organs

It is well known that the main forms of innervation are synapses and free nerve endings, while other forms of innervation have not been reported. Here, we explore a new way of innervating lymphoid organs. Male Sprague‐Dawley rats were used for studying the innervation of sympathetic nerve fibers in lymph nodes by means of anterograde tracking, immunoelectron microscopy, three‐dimension reconstruction analysis, and immunofluorescence labeling. The results showed that the Fluoro‐Ruby labeled nerve endings targeted only a group of cells in the lymph nodes and entered the cells through the plasma membrane. The electron microscopy showed that the biotinylated glucan amine reaction elements were distributed in the cytoplasm, and most of the biotinylated glucan amine active elements were concentrated on the microtubule and microfilament walls. Birbeck particles with rod‐shaped and/or tennis racket like structures can be seen in the labeled cells at high magnification, and Birbeck particles contain biotinylated glucan amine‐reactive elements. The immunofluoresence results showed that the Fluoro‐Ruby‐labeled nerve innervating cells expressed CD207 and CD1a protein. This result confirmed that the labeled cells were Langerhans cells. Our findings suggested that Langerhans cells might serve as a “bridge cell” for neuroimmune cross‐talking in lymph organs, which play an important role in transmitting signals of the nervous system to immune system. This study also opened up a new way for further study of immune regulation mechanism.

[1]  W. Greene,et al.  Immunofluorescence characterization of innervation and nerve-immune cell interactions in mouse lymph nodes , 2019, European journal of histochemistry : EJH.

[2]  K. Nagao,et al.  Langerhans Cells - The Macrophage in Dendritic Cell Clothing. , 2017, Trends in immunology.

[3]  R. B. Kjellerup,et al.  Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment , 2017, Experimental dermatology.

[4]  J. R. de Sousa,et al.  Langerhans cells (CD1a and CD207), dermal dendrocytes (FXIIIa) and plasmacytoid dendritic cells (CD123) in skin lesions of leprosy patients. , 2016, Microbial pathogenesis.

[5]  H. S. Günther,et al.  Dendritic cells and macrophages neurally hard-wired in the lymph node , 2015, Scientific Reports.

[6]  L. Deng,et al.  S100+ cells: A new neuro-immune cross-talkers in lymph organs , 2013, Scientific Reports.

[7]  Kevin J. Tracey,et al.  Neural reflexes in inflammation and immunity , 2012, The Journal of experimental medicine.

[8]  Michael Loran Dustin,et al.  Signaling at neuro/immune synapses. , 2012, The Journal of clinical investigation.

[9]  N. Romani,et al.  Changing views of the role of Langerhans cells. , 2012, The Journal of investigative dermatology.

[10]  M. Amagai,et al.  External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers , 2009, The Journal of experimental medicine.

[11]  A. Braun,et al.  The role of neuro-immune cross-talk in the regulation of inflammation and remodelling in asthma. , 2009, Pharmacology & therapeutics.

[12]  R. Hohlfeld,et al.  Neuro-immune crosstalk in CNS diseases , 2009, Neuroscience.

[13]  D. Nance,et al.  Autonomic innervation and regulation of the immune system (1987–2007) , 2007, Brain, Behavior, and Immunity.

[14]  R. W. Guillery Observations of synaptic structures: origins of the neuron doctrine and its current status , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[15]  M. Mattei,et al.  Identification of Mouse Langerin/CD207 in Langerhans Cells and Some Dendritic Cells of Lymphoid Tissues1 , 2002, The Journal of Immunology.

[16]  G. Chrousos,et al.  The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. , 2000, Pharmacological reviews.

[17]  L. Schmued A rapid, sensitive histochemical stain for myelin in frozen brain sections. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[18]  D. Sachs,et al.  Epidermal Langerhans cells are derived from cells originating in bone marrow , 1979, Nature.

[19]  T. Kobayasi [The Langerhans cells]. , 1975, Ugeskrift for laeger.

[20]  J. Sever,et al.  Birbeck granules (Langerhans' cell granules) in human lymph nodes. , 1973, American journal of clinical pathology.

[21]  K. Jimbow,et al.  Cells containing Langerhans granules in human lymph nodes of dermatopathic lymphadenopathy. , 1969, The Journal of investigative dermatology.

[22]  G. Niebauer,et al.  [ON DENDRITE CELLS IN THE EPIDERMIS. A STUDY ON LANGERHANS CELLS IN NORMAL AND ECZEMATOUS GUINEA PIG SKIN]. , 1965, Archiv fur klinische und experimentelle Dermatologie.

[23]  M. Birbeck,et al.  An Electron Microscope Study of Basal Melanocytes and High-Level Clear Cells (Langerhans Cells) in Vitiligo * , 1961 .

[24]  S. Becker,et al.  Further studies on melanocytes and melanogenesis in the human fetus and newborn. , 1955, The Journal of investigative dermatology.

[25]  P. Langerhans Ueber die Nerven der menschlichen Haut , 1868, Archiv für pathologische Anatomie und Physiologie und für klinische Medicin.

[26]  J. Salamero,et al.  Birbeck granules are subdomains of endosomal recycling compartment in human epidermal Langerhans cells, which form where Langerin accumulates. , 2002, Molecular biology of the cell.

[27]  A. Kukita,et al.  Cells containing Birbeck granules (Langerhans cell granules) in the human thymus. , 1970, Journal of electron microscopy.

[28]  J. Ferreira-Marques [Systema Sensitivum intra epidermicum; the Langerhansian cells as doloriceptores]. , 1951, Archiv fur Dermatologie und Syphilis.