Biology subjects

Chan, B. H. K.

Publications and source records attributed to Chan, B. H. K..

3 recordsLinked to original sources

bioRxiv2025

Migratory dermal gamma delta T cells determine the balance between lung immunity and tissue damage during Nippostrongylus brasiliensis infection

Many helminth parasites migrate through multiple host organs during infection but how immune responses are relayed across these tissues is still poorly understood. To investigate the cellular and molecular aspects of inter-tissue communication during infection we established a percutaneous infection model with the tissue-migrating nematode Nippostrongylus brasiliensis. High-dimension profiling of the initial cutaneous immune response revealed that dermal {gamma}{delta} T cells become activated via an IL-1R-dependent mechanism, engage cell motility-associated transcriptional pathways and leave the skin after parasite invasion. Chemical and genetic inhibition of leukocyte migration prevents the accumulation of IL-17-producing {gamma}{delta} T cells in the lungs. Notably, bypassing the skin phase of infection, and therefore preventing dermal {gamma}{delta} T cell migration, dampens the increase in early IL-17 production in the lungs, and, instead, leads to enhanced IFN-{gamma} responses together with increased lung damage. Collectively, our data highlights a critical skin-lung axis regulating host-parasite interactions and safeguarding lung health.

immunology↗

bioRxiv2022

IL-17A promotes epithelial cell IL-33 production during nematode lung migration

The early migratory phase of pulmonary helminth infections is characterized by tissue injury leading to the release of the alarmin IL-33 and subsequent induction of type 2 immune responses. We recently described a role for IL-17A, through regulation of IFN{gamma}, as an important inducer of type 2 responses during infection with the lung-migrating rodent nematode Nippostrongylus brasiliensis. Here, we aimed to investigate the interaction between IL-17A and IL-33 during the early lung migratory stages of N. brasiliensis infection. In this brief report, we demonstrate that deficiency of IL-17A leads to impaired IL-33 expression and secretion early in infection, independent of IL-17A suppression of IFN{gamma}. Impaired IL-33 production was evident in lung epithelial cells, but not innate immune cells. Therefore, our results demonstrate that IL-17A can drive IL-33 during helminth infection, highlighting an additional mechanism through which IL-17A can regulate pulmonary type 2 immunity.

immunology↗

bioRxiv2021

Maternal γδ T Cells Shape Offspring Pulmonary Type-2 Immunity In A Microbiota-Dependent Manner

Immune system development is greatly influenced by vertically transferred cues. However, beyond antibody-producing B cells, little is known about the role of other cell subsets of the maternal immune system in regulating offspring immunity. We reasoned {gamma}{delta} T cells to be attractive candidates based on their tissue distribution pattern: abundant in the skin, mammary glands and female reproductive tract. Here we found that mice born from {gamma}{delta} T cell-deficient (TCR{delta}-/-) dams display, early after birth, a pulmonary milieu selectively enriched in type-2 cytokines such as IL-33, IL-4, IL-5, and IL-13, and type-2-polarized immune cells, when compared to the progeny of {gamma}{delta} T cell-sufficient dams. In addition, upon helminth infection, mice born from TCR{delta}-/- dams sustained an increased type-2 inflammatory response. Critically, this was independent of the genotype of the pups. Despite similar levels of circulating antibodies in mothers and progeny, the intestinal microbiota in the offspring of TCR{delta}-/- and TCR{delta}+/- dams harbored distinct bacterial communities acquired during birth and fostering. These differences were accompanied by changes in the intestinal short-chain fatty acids (SCFA) profile. Importantly, antibiotic treatment abrogated the differences observed in the pulmonary milieu, and exogenous SCFA supplementation suppressed first-breath- and infection-induced inflammation. In summary, maternal {gamma}{delta} T cells control the establishment of a neonatal gut-lung axis by conditioning the postnatal microbial colonization of the off-spring and bacterial-derived metabolite availability; ultimately impacting on the development of pulmonary type-2 immunity in the offspring.

immunology↗