Langerhans Cells From Mice at Birth Express Endocytic- and Pattern Recognition-Receptors, Migrate to Draining Lymph Nodes Ferrying Antigen and Activate Neonatal T Cells in vivo

Abstract

Antigen capturing at the periphery is one of the earliest, crucial functions of antigenpresenting cells (APCs) to initiate immune responses. Langerhans cells (LCs), the epidermal APCs migrate to draining lymph nodes (DLNs) upon acquiring antigens. An arsenal of endocytic molecules is available to this end, including lectins and pathogen recognition receptors (PRRs). However, cutaneous LCs are poorly defined in the early neonatal period. We assessed endocytic molecules expression in situ: Mannose (CD206)-, Scavenger (SRA/CD204)-, Complement (CD2l, CDllb)-, and Fc-Receptors (CD16/32, CD23) as well as CD1d, CD14, CD205, Langerin (CD207), MHCII, and TLR4 in unperturbed epidermal LCs from both adult and early neonatal mice. As most of these markers were negative at birth (day 0), LC presence was revealed with the conspicuous, epidermal LC-restricted ADPase (and confirmed with CD45) staining detecting that they were as numerous as adult ones. Unexpectedly, most LCs at day 0 expressed CD14 and CD204 while very few were MHCII+ and TLR4+. In contrast, adult LCs lacked all these markers except Langerin, CD205, CD11b, MHCII and TLR4. Intriguingly, the CD204+ and CD14+ LCs predominant at day 0, apparently disappeared by day 4. Upon cutaneous FITC application, LCs were reduced in the skin and a CD204+MHCII+FITC+ population with high levels of CD86 subsequently appeared in DLNs, with a concomitant increased percentage of CD3+CD69+ T cells, strongly suggesting that neonatal LCs were able both to ferry the cutaneous antigen into DLNs and to activate neonatal T cells in vivo. Cell cycle analysis indicated that neonatal T cells in DLNs responded with proliferation. Our study reveals that epidermal LCs are present at birth, but their repertoire of endocytic molecules and PRRs differs to that of adult ones. We believe this

The roles of tissue resident macrophages in health and cancer

“…In contrast to human LCs, mouse LCs lack CD205 and CD207 expression, and instead express CD14, CD204, and low levels of MHCII and TLR4 molecules at birth. Intriguingly y, the CD204 + and CD14 + LCs disappear after four days, and MHCII, CD11c, and CD207 are acquired during the first week of life [ 198 ].…”

Dissociation protocols influence the phenotypes of lymphocyte and myeloid cell populations isolated from the neonatal lymph node

“…External factors such as bacterial exposure ( 31 ) and colonization ( 32 ), as well as internal factors such as organ development and growth ( 33 , 34 ), are thought to influence immune development. Important questions remain regarding how age ( 35 , 36 ) and exposure ( 12 , 37 ) influence the diverse subsets and functions of APCs and their impact on adaptive immunity ( 37 – 39 ).…”

Have We Ignored Vector-Associated Microbiota While Characterizing the Function of Langerhans Cells in Experimental Cutaneous Leishmaniasis?

“…Solid symbols represent a possible interaction between PRRs and LM-PAMPs. Keratinocytes(49)(50)(51)(52)(53), Fibroblasts(54)(55)(56)(57)(58), TLR8(54,59), Neutrophil granulocytes(60)(61)(62)(63)(64)(65)(66)(67)(68)(69), Epidermal Langerhans cells(24,(70)(71)(72)(73). Dermal Macrophages(69,74,75).…”