PMID- 34038479
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 5
DP  - 2021
TI  - Peripheral blood basophils are the main source for early interleukin-4 secretion 
      upon in vitro stimulation with Culicoides allergen in allergic horses.
PG  - e0252243
LID - 10.1371/journal.pone.0252243 [doi]
LID - e0252243
AB  - Interleukin-4 (IL-4) is a key cytokine secreted by type 2 T helper (Th2) cells 
      that orchestrates immune responses during allergic reactions. Human and mouse 
      studies additionally suggest that basophils have a unique role in the regulation 
      of allergic diseases by providing initial IL-4 to drive T cell development 
      towards the Th2 phenotype. Equine Culicoides hypersensitivity (CH) is a seasonal 
      immunoglobulin E (IgE)-mediated allergic dermatitis in horses in response to 
      salivary allergens from Culicoides (Cul) midges. Here, we analyzed IL-4 
      production in peripheral blood mononuclear cells (PBMC) of CH affected (n = 8) 
      and healthy horses (n = 8) living together in an environment with natural Cul 
      exposure. During Cul exposure when allergic horses had clinical allergy, IL-4 
      secretion from PBMC after stimulation with Cul extract was similar between 
      healthy and CH affected horses. In contrast, allergic horses had higher IL-4 
      secretion from PBMC than healthy horses during months without allergen exposure. 
      In addition, allergic horses had increased percentages of IL-4+ cells after Cul 
      stimulation compared to healthy horses, while both groups had similar percentages 
      of IL-4+ cells following IgE crosslinking. The IL-4+ cells were subsequently 
      characterized using different cell surface markers as basophils, while very few 
      allergen-specific CD4+ cells were detected in PBMC after Cul extract stimulation. 
      Similarly, IgE crosslinking by anti-IgE triggered basophils to produce IL-4 in 
      all horses. PMA/ionomycin consistently induced high percentages of IL-4+ Th2 
      cells in both groups confirming that T cells of all horses studied were capable 
      of IL-4 production. In conclusion, peripheral blood basophils produced high 
      amounts of IL-4 in allergic horses after stimulation with Cul allergens, and 
      allergic horses also maintained higher basophil percentages throughout the year 
      than healthy horses. These new findings suggest that peripheral blood basophils 
      may play a yet underestimated role in innate IL-4 production upon allergen 
      activation in horses with CH. Basophil-derived IL-4 might be a crucial early 
      signal for immune induction, modulating of immune responses towards Th2 immunity 
      and IgE production.
FAU - Raza, Fahad
AU  - Raza F
AD  - Departments of Population Medicine and Diagnostic Sciences, College of Veterinary 
      Medicine, Cornell University, Ithaca, New York, United States of America.
FAU - Babasyan, Susanna
AU  - Babasyan S
AD  - Departments of Population Medicine and Diagnostic Sciences, College of Veterinary 
      Medicine, Cornell University, Ithaca, New York, United States of America.
FAU - Larson, Elisabeth M
AU  - Larson EM
AD  - Departments of Population Medicine and Diagnostic Sciences, College of Veterinary 
      Medicine, Cornell University, Ithaca, New York, United States of America.
FAU - Freer, Heather S
AU  - Freer HS
AD  - Departments of Population Medicine and Diagnostic Sciences, College of Veterinary 
      Medicine, Cornell University, Ithaca, New York, United States of America.
FAU - Schnabel, Christiane L
AU  - Schnabel CL
AD  - Departments of Population Medicine and Diagnostic Sciences, College of Veterinary 
      Medicine, Cornell University, Ithaca, New York, United States of America.
FAU - Wagner, Bettina
AU  - Wagner B
AUID- ORCID: 0000-0003-2370-6324
AD  - Departments of Population Medicine and Diagnostic Sciences, College of Veterinary 
      Medicine, Cornell University, Ithaca, New York, United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210526
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Allergens)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Allergens/*pharmacology
MH  - Animals
MH  - Basophils/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Ceratopogonidae/immunology
MH  - Horses
MH  - Interleukin-4/*metabolism
MH  - Phenotype
PMC - PMC8153460
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/05/27 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/05/26
CRDT- 2021/05/26 17:40
PHST- 2020/11/13 00:00 [received]
PHST- 2021/05/11 00:00 [accepted]
PHST- 2021/05/26 17:40 [entrez]
PHST- 2021/05/27 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/05/26 00:00 [pmc-release]
AID - PONE-D-20-35825 [pii]
AID - 10.1371/journal.pone.0252243 [doi]
PST - epublish
SO  - PLoS One. 2021 May 26;16(5):e0252243. doi: 10.1371/journal.pone.0252243. 
      eCollection 2021.