Project description:Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens, allergens, tissue remodeling and metabolic homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated but co-receptor mediated negative regulatory axis is yet to be defined. We demonstrate that PD-1 is an important negative regulator of KLRG1+ILC-2 function in both mice and humans. Increase in KLRG1+ ILC-2 cells numbers were attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1+ ILC-2 subsets occurred in pdcd1-/- mice and on adoptive transfer, pdcd1-/- KLRG1+ ILC-2s significantly reduced worm burden. Furthermore, blocking antibody to PD-1 increased KLRG1+ ILC-2 cell number and reduced disease burden. Therefore PD-1 is an important negative regulator and is vital for maintaining the number and hence function of KLRG1+ ILC-2s.
Project description:A transitory, interleukin-25-responsive, KLRG1high Group 2 innate lymphoid (ILC2) cell subset that migrates to mucosal tissues early during type-2 inflammation was recently identified. This study focuses on understanding the significance of this population in relation to tissue-resident ILC2 cells in the lung and intestine. RNA-sequencing and unbiased pathway analysis revealed the AP-1 factor BATF as a potential modulator of ILC2 cell fate. For RNAseq, KLRG1-postive and KLRG1-neagive populations were sorted and compared.
Project description:The importance of unanchored Ub in innate immunity has been shown only for a limited number of unanchored Ub-interactors. We investigated what additional cellular factors interact with unanchored Ub and whether unanchored Ub plays a broader role in innate immunity. To identify unanchored Ub-interacting factors from murine lungs, we used His-tagged recombinant poly-Ub chains as bait. These chains were mixed with lung tissue lysates and protein complexes were isolated with Ni-NTA beads. Sample elutions were subjected to mass spectrometry (LC-MSMS) analysis.