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UID:20250725T184448EDT-8037IazkkT@132.216.98.100
DTSTAMP:20250725T224448Z
DESCRIPTION:\n	Immune cells are the only cells in the body able to migrate b
 oth between and within tissues. The importance of immune cell movement to 
 immune system function is well illustrated in instances where mutations th
 at impair migration cause immunodeficiency. In humans\, loss-of-function m
 utations in DOCK8\, which encodes for a guanine exchange factor involved i
 n hematopoietic cell migration\, lead to severe lymphopenia and\, paradoxi
 cally\, a high incidence of allergic disease\, which is driven by type 2 C
 D4+ helper T (Th2) cells. We demonstrate that\, like humans\, Dock8-/- mic
 e have a profound Th2 cell bias upon pulmonary infection with Cryptococcus
  neoformans or influenza A virus. We show that recruited Dock8-/- CX3CR1+ 
 mononuclear phagocytes are exquisitely sensitive to migration-induced cell
  shattering\, activating caspase-1 and -3 and releasing interleukin (IL)-1
 β. Inhibiting IL-1β or caspase activation eliminates the type-2 skew in Do
 ck8-deficient mice. Importantly\, treating infected Dock8-/- mice that wer
 e given a pan-caspase inhibitor with exogenous IL-1b did not recapitulate 
 the Th2 skew\, indicating that IL-1b is necessary but not sufficient in th
 e type-2 bias. Thus\, we implicate an additional caspase-dependent co-sign
 al in the Th2 skew. Remarkably\, treatment of wild-type mice with dying ce
 lls during infection induced a type-2 biased CD4 T cell response\, indicat
 ing that cell death favors Th2 differentiation even in a Dock8-sufficient 
 context. Interestingly\, we also find that unlike upon mucosal infections\
 , systemic infection with lymphocytic choriomeningitis virus of Dock8-/- m
 ice leads to a Th2 biased response in barrier tissues\, but not in non-bar
 rier organs\, suggesting there are additional tissue-specific differences 
 that permit the development of allergic pathology only in barrier surfaces
 . Together\, our work reveals an important role for cell death and the tis
 sue microenvironment in the etiology of Th2 responses\, which may have imp
 lications for understanding the induction and rise of allergic diseases.\n
DTSTART:20220429T150000Z
DTEND:20220429T160000Z
LOCATION:Room 1034\, McIntyre Medical Building\, CA\, QC\, Montreal\, H3G 1
 Y6\, 3655 promenade Sir William Osler
SUMMARY:Seminar - From beyond the grave: cell death and type-2 helper T cel
 l differentiation
URL:/physiology/channels/event/seminar-beyond-grave-ce
 ll-death-and-type-2-helper-t-cell-differentiation-338586
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