page_title: Innate lymphoid cell
section_title: Lymphoid Tissue inducer (LTi) cells
hierarchical_section_title: Innate lymphoid cell / Classification / Lymphoid Tissue inducer (LTi) cells
caption_attribution_description: English: LTi phenotypic markers.
context_page_description: Innate lymphoid cells are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors. In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the peripheral blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the absence of regular lymphoid morphology, rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.
  Based on the difference in developmental pathways, phenotype, and signalling molecules produced, in 2013, ILCs were divided into three groups: 1, 2 and 3, however, after further investigation, we now appreciate five distinct subsets within these groups: NK cells, ILC1s, ILC2s, ILC3s, and LTi cells.
context_section_description: LTi cells are considered a separate lineage due to their unique developmental pathway, however, they are often considered part of the ILC3 group as they have many similar characteristics. Like ILC3s, LTi cells are dependent on RORγt. They are involved in the formation of secondary lymph nodes, and Peyer’s patches, by promoting lymphoid tissue development, through the action of lymphotoxin, a member of the  TNF superfamily. They are critical during both the embryonic and adult stages of development of the immune system, and therefore LTi cells are present in organs and tissues early during embryonal development. They have a pivotal role in primary and secondary lymphoid tissue organisation, and in adult lymphoid tissue, regulating the adaptive immune response and maintaining secondary lymphoid tissue structures. 
  Their production is stimulated upon retinoic acid, CXCL13, RANK-L, and the cytokines: IL-1B, IL-23, and IL-6. They express c- Kit, CCR6, CD25, CD127, and CD90, however, no NCRs. The expression of OX40L is another good marker for LTi cells in adult mice and humans. They can be CD4+/-.  Like ILC3s, upon activation, LTi cells mostly produce IL-17A, IL-17F, and IL-22. They are mediated by RANK, TNF, IL-17, and IL-22.
  LTi cells induce the expression of AIRE, the autoimmune regulatory gene, by allowing development of embryonic thymic epithelial cells.  They do this via lymphotoxin α4β7 and RANK-L signalling.  LTi cells also allow the survival of memory CD4+ T cells, and therefore memory immune responses, within newly formed lymph nodes. They do this via the TNF superfamily members OX40L and CD30L, which signal to the CD4+ T cells. This role could be used to prevent autoimmunity, and to enhance memory responses after vaccination.
caption: The different phenotypic markers present on LTi cells present in an embryo and an adult.[23]
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