Lymphoid Tissue Inducer-A Divergent Member of the ILC Family

Overview

Journal Cytokine Growth Factor Rev

Date 2018 Feb 19

PMID 29454785

Citations 32

Authors

Chao Zhong

Mingzhu Zheng

Jinfang Zhu

Affiliations

Soon will be listed here.

Abstract

Innate lymphoid cells (ILCs) that are capable of producing effector cytokines reminiscent of CD4 T helper (Th) cells during infections and tissue inflammations have drawn much attention in the immunology field in recent years. Within the ILCs, the lymphoid tissue inducer (LTi) cells that play a critical role in lymphoid organogenesis were identified long before the establishment of the ILC concept. LTi cells, developed and functioning mainly at the fetal stage, and LTi-like cells, presumably generated during the adulthood, are regarded as a subset of type 3 ILCs (ILC3s) because they express the ILC3 lineage-defining transcription factor RORγt, and like other ILC3s, can produce an ILC3 signature cytokine IL-22 and initiate protective immune responses against extracellular bacteria. However, LTi/LTi-like cells have a unique gene expression pattern, and they develop from a progenitor that is distinct from the progenitor of all other ILCs and the progenitor of conventional natural killer (cNK) cells. There are also several other unique features of LTi/LTi-like cells comparing to non-LTi ILC3s. In addition to their classical function in lymphoid organogenesis, LTi/LTi-like cells also have specialized functions in association with the adaptive immune system, which include their effects on T and B cell development, activation and function. In this review, we summarize these specific features of LTi/LTi-like cells and propose that these cells should be considered as a separated innate lymphoid lineage in parallel with other non-LTi ILCs and cNK cells.

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References

Kim M, Anderson G, White A, Jenkinson E, Arlt W, Martensson I . OX40 ligand and CD30 ligand are expressed on adult but not neonatal CD4+CD3- inducer cells: evidence that IL-7 signals regulate CD30 ligand but not OX40 ligand expression. J Immunol. 2005; 174(11):6686-91. DOI: 10.4049/jimmunol.174.11.6686. View

Rossi S, Kim M, Leibbrandt A, Parnell S, Jenkinson W, Glanville S . RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med. 2007; 204(6):1267-72. PMC: 2118623. DOI: 10.1084/jem.20062497. View

Ohne Y, Silver J, Thompson-Snipes L, Collet M, Blanck J, Cantarel B . IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity. Nat Immunol. 2016; 17(6):646-55. DOI: 10.1038/ni.3447. View

Ibiza S, Garcia-Cassani B, Ribeiro H, Carvalho T, Almeida L, Marques R . Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature. 2016; 535(7612):440-443. PMC: 4962913. DOI: 10.1038/nature18644. View

Fuchs A, Vermi W, Lee J, Lonardi S, Gilfillan S, Newberry R . Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells. Immunity. 2013; 38(4):769-81. PMC: 3634355. DOI: 10.1016/j.immuni.2013.02.010. View

Constantinides M, McDonald B, Verhoef P, Bendelac A . A committed precursor to innate lymphoid cells. Nature. 2014; 508(7496):397-401. PMC: 4003507. DOI: 10.1038/nature13047. View

Cazac B, Roes J . TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo. Immunity. 2000; 13(4):443-51. DOI: 10.1016/s1074-7613(00)00044-3. View

Finke D, Acha-Orbea H, Mattis A, Lipp M, Kraehenbuhl J . CD4+CD3- cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5. Immunity. 2002; 17(3):363-73. DOI: 10.1016/s1074-7613(02)00395-3. View

Fang D, Zhu J . Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets. J Exp Med. 2017; 214(7):1861-1876. PMC: 5502437. DOI: 10.1084/jem.20170494. View

10.

ROGERS P, Song J, Gramaglia I, Killeen N, Croft M . OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity. 2001; 15(3):445-55. DOI: 10.1016/s1074-7613(01)00191-1. View

11.

Magri G, Miyajima M, Bascones S, Mortha A, Puga I, Cassis L . Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells. Nat Immunol. 2014; 15(4):354-364. PMC: 4005806. DOI: 10.1038/ni.2830. View

12.

Geiger T, Abt M, Gasteiger G, Firth M, OConnor M, Geary C . Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. J Exp Med. 2014; 211(9):1723-31. PMC: 4144732. DOI: 10.1084/jem.20140212. View

13.

Zhou L, Chong M, Littman D . Plasticity of CD4+ T cell lineage differentiation. Immunity. 2009; 30(5):646-55. DOI: 10.1016/j.immuni.2009.05.001. View

14.

Fallon P, Ballantyne S, Mangan N, Barlow J, Dasvarma A, Hewett D . Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med. 2006; 203(4):1105-16. PMC: 2118283. DOI: 10.1084/jem.20051615. View

15.

Gaspal F, Kim M, McConnell F, Raykundalia C, Bekiaris V, Lane P . Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory. J Immunol. 2005; 174(7):3891-6. DOI: 10.4049/jimmunol.174.7.3891. View

16.

von Burg N, Chappaz S, Baerenwaldt A, Horvath E, Bose Dasgupta S, Ashok D . Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses. Proc Natl Acad Sci U S A. 2014; 111(35):12835-40. PMC: 4156721. DOI: 10.1073/pnas.1406908111. View

17.

Hashi H, Yoshida H, Honda K, Fraser S, Kubo H, Awane M . Compartmentalization of Peyer's patch anlagen before lymphocyte entry. J Immunol. 2001; 166(6):3702-9. DOI: 10.4049/jimmunol.166.6.3702. View

18.

Delconte R, Shi W, Sathe P, Ushiki T, Seillet C, Minnich M . The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15. Immunity. 2016; 44(1):103-115. DOI: 10.1016/j.immuni.2015.12.007. View

19.

Mebius R, Rennert P, Weissman I . Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity. 1997; 7(4):493-504. DOI: 10.1016/s1074-7613(00)80371-4. View

20.

van de Pavert S, Mebius R . New insights into the development of lymphoid tissues. Nat Rev Immunol. 2010; 10(9):664-74. DOI: 10.1038/nri2832. View