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The interleukin (IL)-17 family, consisting of six members, promotes host defense but can in some context promote the development of autoimmune disease. Here, we examined the role of IL-17D, a poorly understood member in the IL-17 family. IL-17D was expressed primarily by colonic epithelial cells. Il17d -/- mice were more susceptible to acute colitis, bacterial infection and experimentally induced colon cancer than their wildtype counterparts. Il17d deficiency impaired IL-22 production by group 3 innate lymphoid cells (ILC3s) and reduced expression of IL-22-dependent antimicrobial peptides, RegIIIβ and RegIIIγ, in colon tissue at steady state and in colitis; this was associated with changes in microbial composition and dysbiosis. Protein purification studies revealed that IL-17D bound not canonical IL-17 receptors, but rather CD93, a glycoprotein expressed on mature ILC3s. Mice lacking Cd93 in ILC3s exhibited impaired IL-22 production and aggravated colonic inflammation in experimental colitis. Thus, an IL-17D-CD93 axis regulates ILC3 function to preserve intestinal homeostasis., Competing Interests: Declaration of interests J.L.H., X.H.W., and C.D. have filed a provisional patent disclosure based on the results in the paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Questions regarding T cell development have recently received much attention, but the earliest intrathymic differentiation steps in adult mice have remained controversial. Three new papers together show that for at least some thymus-settling precursors, the loss of B lineage potential occurs in the thymus, and Notch acts on multipotent progenitors early after thymic entry.

Lymphocyte activation via antigen receptors initiates adaptive immune responses. Two papers in this issue of Immunity demonstrate that CARMA-1, a CARD carrying member of the MAGUK family proteins, is essential for lymphocyte activation. CARMA-1 functions by coupling antigen receptor signals to NF-kappaB induction and JNK activation.

In this paper the potential of flow-fluorometric DNA determination as a convenient and economical alternative to conventional cytogenetics for the diagnosis of aneuploidy in human lymphocytes is explored. By comparing euploid and aneuploid samples, we found that the fluorescence signals emitted from propidium iodide (PI) stained cells are linearly proportional to DNA content. Variation in DNA content between euploid individuals of a given sex was sufficiently low to permit diagnosis of aneuploidy involving chromosomes with greater than 1.8% of the total diploid DNA (e.g., X, 8, 9, and 13). Interindividual DNA content variation with flow fluorometry was too substantial, however, to confidently diagnose trisomy 21. Fluorescent stains which exclude (variant) simple sequence DNA might overcome this limitation.

Although regulatory T cells protect people from autoimmunity, two recent papers in Immunity ( Malchow et al., 2016; Kieback et al., 2016 ) demonstrate that these cells are also a crisis averted. Without the proper education in the thymus, these cells will turn on their host and cause autoimmunity. [ABSTRACT FROM AUTHOR]

Lymphocytes are covered with sugars. Some of the oligosaccharides on lymphocytes may be recognized by specific lectins such as the selectins, but what other functions do all of these oligosaccharides serve? Two recent papers in Cell and Immunity describe a novel role for glycosylation in the thymus—regulating the interaction of MHC class I molecules with CD8 during thymocyte maturation. [Copyright &y& Elsevier]

T follicular cells help B cells generate high-affinity antibodies. Two papers in this issue of Immunity (, and ) have identified a role for interleukin-21 in the development of these specialized cells and highlight questions about how this dedicated population is generated. [Copyright &y& Elsevier]

In a recent paper in Nature, show that the immunoreceptor PD-1 is upregulated by “exhausted” T cells during the chronic phase of viral infection in mice. Remarkably, blocking the interaction between PD-1 and its ligand, PD-L1, reactivates these T cells and reduces viral load. [Copyright &y& Elsevier]

A paper by in this issue of Immunity examines the mechanisms used by granzyme A to kill target cells after its cytoplasmic injection by cytotoxic lymphocytes. They show that this protease induces mitochondrial damage and generation of reactive oxygen species that are necessary for cell death. [Copyright &y& Elsevier]