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Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth response that mobilizes and remodels the intestinal tissue for effector function; however, there is growing appreciation of the impact GIN infection also has on the distal tissue immune state. Indeed, this effect is observed even in tissues through which GINs never transit. This review highlights how GIN infection modulates systemic immunity through (a) induction of host resistance and tolerance responses, (b) secretion of immunomodulatory products, and (c) interaction with the intestinal microbiome. It also discusses the direct consequences that changes to distal tissue immunity can have for concurrent and subsequent infection, chronic noncommunicable diseases, and vaccination efficacy. [ABSTRACT FROM AUTHOR]

The article explores how Follicular helper T (TFH) cells are essential for generating protective humoral immunity. Topics discussed include thymocyte selection–associated HMG-box protein (TOX) was identified as a central transcription regulator in TFH cell development; TOX promotes the expression of multiple molecules that play critical roles in TFH cell differentiation and function; and understanding of the molecular mechanisms that govern the differentiation and function of TFH cells.

During thymocyte development, medullary thymic epithelial cells (mTECs) provide appropriate instructive cues in the thymic microenvironment for not only negative selection but also the generation of regulatory T (T reg) cells. Here, we identify that miR-155, a microRNA whose expression in T reg cells has previously been shown to be crucial for their development and homeostasis, also contributes to thymic T reg (tT reg) cell differentiation by promoting mTEC maturation. Mechanistically, we show that RANKL stimulation induces expression of miR-155 to safeguard the thymic medulla through targeting multiple known and previously uncharacterized molecules within the TGFβ signaling pathway, which is recognized for its role in restricting the maturation and expansion of mTECs. Our work uncovers a miR-155-TGFβ axis in the thymic medulla to determine mTEC maturity and, consequently, the quantity of tT reg cells and suggests that miR-155 ensures proper tT reg cell development in both cell-intrinsic and -extrinsic manners., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Dong et al.)

Follicular helper T (T FH ) cells are essential for generating protective humoral immunity. To date, microRNAs (miRNAs) have emerged as important players in regulating T FH cell biology. Here, we show that loss of miR-23~27~24 clusters in T cells resulted in elevated T FH cell frequencies upon different immune challenges, whereas overexpression of this miRNA family led to reduced T FH cell responses. Mechanistically, miR-23~27~24 clusters coordinately control T FH cells through targeting a network of genes that are crucial for T FH cell biology. Among them, thymocyte selection-associated HMG-box protein (TOX) was identified as a central transcription regulator in T FH cell development. TOX is highly up-regulated in both mouse and human T FH cells in a BCL6-dependent manner. In turn, TOX promotes the expression of multiple molecules that play critical roles in T FH cell differentiation and function. Collectively, our results establish a key miRNA regulon that maintains optimal T FH cell responses for resultant humoral immunity., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)